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[gamma]-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adult central nervous system (CNS) synapses, but it excites immature CNS neurons as well as neurons in the myenteric plexus. The present work aimed to determine whether GABA-induced nonadrenergic, noncholinergic (NANC) neuronal-mediated relaxation of the rat duodenum is dependent on the activity of [Na.sup.+] [K.sup.+] [Cl.sup.-] cotransporters (NKCC) and requires calcium influx. In the presence of guanethidine (3 [micro]mol/L), atropine (3 [micro]mol/L), and indomethacin (1 [micro]mol/L), relaxations induced by GABA (100 [micro]mol/L), KCl (5-10 mmol/L) and electrical field stimulation (1-8 Hz, 2 ms, 60 V), but not those induced by bradykinin (10-100 nmol/L) were abolished by lidocaine (300 [micro]mol/L). However, only GABA-induced relaxations were reduced in a concentration-dependent manner by the NKCC1/2 inhibitors bumetanide (0.1-1 [micro]mol/L) and furosemide (1-10 [micro]mol/L). GABA-induced NANC neuronal relaxation was abolished by bicuculline (30 [micro]mol/L) and inhibited by N-nitroarginine methyl ester (L-NAME, 300 [micro]mol/L). The [omega]- conotoxin GVIA (1 pmol/L), which acts exclusively on neuronal CaV2 channels, but not on smooth muscle voltage-gated [Ca.sup.2+] [Ca.sub.V]1 channels, and nonselective blockers of these channels (verapamil 100 nmol/L and ruthenium red 10 [micro]mol/L), reduced GABA-induced relaxations. These results showed that the activation of [GABA.sub.A] receptors induces NANC nitrergic neuronal relaxations in the rat duodenum, which depend on NKCC activity and [CaV.sub.2] channel activation, suggesting that this phenomenon results from neuronal depolarization promoted by [Cl.sup.-] efflux through GABAa receptors, with subsequent [Ca.sup.2+] influx and nitric oxide release. Key words: GABA, NKCC cotransporters, NANC neurons, rat duodenum, nitric oxide and [Ca.sup.2+] Le GABA constitue le principal neurotransmetteur inhibiteur dans les synapses du SNC adulte, mais il joue un role excitateur dans les neurones du SNC immature, de meme que dans les neurones du plexus myenterique. Les presents travaux visaient a etablir si la relaxation du duodenum de rat mediee par le GABA dans les neurones non adrenergiques, non cholinergiques (NANC) est dependante de l'activite des cotransporteurs NKCC et si elle necessite un flux entrant de calcium. En presence de guanethidine (3 [micro]M), d'atropine (3 [micro]M) et d'indometacine (1 [micro]M), les relaxations obtenues avec le GABA (100 [micro]M), le KCl (5-10 mM) et la stimulation en champ electrique (SCE, 1-8 Hz, 2 ms, 60 V) etaient abolies avec la lidocaine (300 [micro]M), mais pas celles obtenues avec la bradykinine (10-100 [micro]M). Toutefois, uniquement les relaxations obtenues avec le GABA diminuaient de maniere proportionnelle a la concentration de bumetanide (0,1-1 [micro]M) et de furosemide (1-10 [micro]M), inhibiteurs des NKCC1/2. Les relaxations obtenues avec le GABA par les neurones NANC etaient abolies en presence de bicuculline (30 [micro]M) et inhibees en presence de l-NAME (300 [micro]M). L'[omega]-conotoxine-GVIA (1 [micro]M) (qui agit uniquement sur les canaux CaV2 neuronaux et pas sur les canaux [Ca.sup.2+] voltage-dependants CaV1 dans le muscle lisse) et des bloqueurs non selectifs de ces canaux (verapamil a 100 nM et rouge de ruthenium a 10 [micro]M) entrainaient une diminution des relaxations obtenues avec le GABA. Ces resultats montrent que dans le duodenum de rat, l'activation des recepteurs GABAA entraine des relaxations neuronales NANC nitrergiques, qui dependent de l'activite de NKCC et de l'activation des canaux CaV2, ce qui laisse entendre que ce phenomene proviendrait d'une depolarisation neuronale favorisee par le flux sortant d'ions [Cl.sup.-] par les recepteurs GABAA, avec ensuite un flux entrant d'ions [Ca.sup.2+] et la liberation d'oxyde nitrique. [Traduit par la Redaction] Mots-cles : GABA, cotransporteurs NKCC, neurones NANC, duodenum de rat, oxyde nitrique et ions [Ca.sup.2+]., Introduction Since the 1960s, countless studies have pointed to the participation of intrinsic inhibitory nerves in the relaxation of intestinal smooth muscle. These nerves make up the nonadrenergic, noncholinergic (NANC) [...]

Presence of taste receptor families in the gastrointestinal mucosa suggests a physiological basis for local and early detection of a meal. We hypothesized that luminal L-glutamate, which is the primary nutrient conferring fundamental umami or proteinaceous taste, influences mucosal defense mechanisms in rat duodenum. We perfused the duodenal mucosa of anesthetized rats with L-glutamate (0.1-10 mM). Intracellular pH ([pH.sub.i]) of the epithelial cells, blood flow, and mucus gel thickness (MGT) were simultaneously and continuously measured in vivo. Some rats were pretreated with indomethacin or capsaicin. Duodenal bicarbonate secretion (DBS) was measured with flow-through pH and C[O.sub.2] electrodes. We tested the effects of agonists or antagonists for metabotropic glutamate receptor (mGluR) 1 or 4 or calcium-sensing receptor (CaSR) on defense factors. Luminal L-glutamate dose dependently increased [pH.sub.i] and MGT but had no effect on blood flow in the duodenum. L-glutamate (10 mM)-induced cellular alkalinization and mucus secretion were inhibited by pretreatment with indomethacin or capsaicin. L-glutamate effects on [pH.sub.i] and MGT were mimicked by mGluR4 agonists and inhibited by an mGluR4 antagonist. CaSR agonists acidified cells with increased MGT and DBS, unlike L-glutamate. Perfusion of L-glutamate with inosinate (inosine 5'-monophosphate, 0.1 mM) enhanced DBS only in combination, suggesting synergistic activation of the L-glutamate receptor, typical of taste receptor type 1. L-leucine or L-aspartate had similar effects on DBS without any effect on [pH.sub.i] and MGT. Preperfusion of L-glutamate prevented acid-induced cellular injury, suggesting that L-glutamate protects the mucosa by enhancing mucosal defenses. Luminal L-glutamate may activate multiple receptors and afferent nerves and locally enhance mucosal defenses to prevent subsequent injury attributable to acid exposure in the duodenum. intracellular alkalinization; mucus secretion; bicarbonate secretion; monosodium glutamate; taste receptor doi: 10.1152/ajpgi.90605.2008

Presence of appetite-regulating peptides orexin-A and orexin-B in mucosal endocrine cells suggests a role in physiological control of the intestine. Our aim was to characterize orexin-induced stimulation of duodenal bicarbonate secretion and modulation of secretory responses and mucosal orexin receptors by overnight food deprivation. Lewis x Dark Agouti rats were anesthetized and proximal duodenum cannulated in situ. Mucosal bicarbonate secretion (pH stat) and mean arterial blood pressure were continuously recorded. Orexin-A was administered intra-arterially close to the duodenum, intraluminally, or into the brain ventricles. Total RNA was extracted from mucosal specimens, reverse transcribed to eDNA and expression of orexin receptors 1 and 2 (OX1 and OX2) measured by quantitative real-time PCR. OX1 protein was measured by Western blot. Intra-arterial orexin-A (60-600 nmol*[h.sup.-1] * [kg.sup.-1]) increased (P < 0.01) the duodenal secretion in fed but not in fasted animals. The OX1 receptor antagonist SB-334867, which was also found to have a partial agonist action, abolished the orexin-induced secretory response but did not affect secretion induced by the muscarinic agonist bethanechol. Atropine, in contrast, inhibited bethanechol but not orexin-induced secretion. Orexin-A infused into the brain ventricles (2-20 nmol*[kg.sup.-1]*[h.sup.-1]) or added to luminal perfusate (1.0-100 nM) did not affect secretion, indicating that orexin-A acts peripherally and at basolateral receptors. Overnight fasting decreased mucosal OX1 and OX2 mRNA expression (P < 0.01) as well as OX1 protein expression (P < 0.05). We conclude that stimulation of secretion by orexin-A may involve both receptor types and is independent of cholinergic pathways. Intestinal OX receptors and secretory responses are markedly related to food intake. bicarbonate secretion; enteroendocrine cells; fed and fasting state; perfused duodenum in situ; TRH

Chronic metabolic acidosis results in a negative calcium balance as a result of bone resorption and renal calcium loss. However, reports on the changes in intestinal calcium transport have been controversial. The present investigation therefore aimed to study the effects of chronic metabolic acidosis induced by 1.5% N[H.sub.4]Cl administration on the three components of duodenal calcium transport, namely, solvent drag-induced, transcellular active, and passive paracellular components, in rats using an in vitro Ussing chamber technique. The relative mRNA expression of genes related to duodenal calcium transport was also determined. We found that 21-day chronic metabolic acidosis stimulated solvent drag-induced and transcellular active duodenal calcium transport but not passive paracellular calcium transport. Our results further demonstrated that an acute direct exposure to serosal acidic pH, in contrast, decreased solvent drag-induced calcium transport in a pH-dependent fashion but had no effect on transcellular active calcium transport. Neither the transepithelial resistance nor duodenal permeability to [Na.sup.+], [Cl.sup.-], and [Ca.sup.2+] via the passive paracellular pathway were altered by chronic metabolic acidosis, suggesting that widening of the tight junction and changes in the charge-selective property of the tight junction did not occur. Thus the enhanced duodenal calcium transport observed in chronic metabolic acidosis could have resulted from a long-term adaptation, possibly at the molecular level. RT-PCR study revealed that chronic metabolic acidosis significantly increased the relative mRNA expression of duodenal genes associated with solvent drag-induced transport, i.e., the [[beta].sub.1]-subunit of [Na.sup.+]-[K.sup.+]-ATPase, zonula occludens-1, occludin, and claudin-3, and with transcellular active transport, i.e., transient receptor potential vanilloid family [Ca.sup.2+] channels 5 and 6 and plasma membrane [Ca.sup.2+]-ATPase isoform 1b. Total plasma calcium and free ionized calcium and magnesium concentrations were also increased, whereas serum parathyroid hormone and 1[alpha],25-dihydroxyvitamin [D.sub.3] levels were not changed. The results indicated that 21-day chronic metabolic acidosis affected the calcium metabolism in rats partly through enhancing the mRNA expression of crucial duodenal genes involved in calcium absorption, thereby stimulating solvent drag-induced and transcellular active calcium transport in the duodenum. tight junction; dilution potential; N[H.sub.4]Cl; trifluorperazine; Ussing chamber doi:10.1152/ajpgi.00108.2006

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is an important pathway for duodenal mucosal bicarbonate secretion. Duodenal biopsies from CF patients secrete bicarbonate in response to heat-stable enterotoxin from Escherichia coli (STa) but not cAMP. To explore the mechanism of STa-induced bicarbonate secretion in CF more fully, we examined the role of CFTR in STa-stimulated duodenal bicarbonate secretion in mice. In vivo, the duodenum of CFTR (-/-) or control mice was perfused with forskolin ([10.sup.-4] M), STa ([10.sup.-7] M), uroguanylin ([10.sup.-7] M), 8-bromoguanosine 3',5'-cGMP (8-Br-cGMP) ([10.sup.-3] M), genistein ([10.sup.-6] M) plus STa, or herbimycin A ([10.sup.-6] M) plus STa. In vitro, duodenal mucosae were voltage-clamped in Ussing chambers, and bicarbonate secretion was measured by pH-stat. The effect of genistein, DIDS ([10.sup.-4] M), and chloride removal was also studied in vitro. Control, but not CF, mice produced a significant increase in duodenal bicarbonate secretion after perfusion with forskolin, uroguanylin, or 8-Br-cGMP. However, both control and CF animals responded to STa with significant increases in bicarbonate output. Genistein and herbimycin A abolished this response in CF mice but not in controls. In vitro, STa-stimulated bicarbonate secretion in CF tissues was inhibited by genistein, DIDS, and chloride-free conditions, whereas bicarbonate secretion persisted in control mice. In the CF duodenum, STa can stimulate bicarbonate secretion via tyrosine kinase activity resulting in apical [Cl.sup.-]/HC[O.sup.-.sub.3] exchange. Further studies elucidating the intracellular mechanisms responsible for such non-CFTR mediated bicarbonate secretion may lead to important therapies for CF. tyrosine kinase; cystic fibrosis; chloride/bicarbonate exchange

The aim of this study was to develop a new method for investigation of the relationship among the mechanical stimulus, the biomechanical properties, and the visceral perception evoked by volume/ramp-controlled distension in the human duodenum in vivo. An impedance planimetric probe for balloon distension, was placed in the third part of the duodenum in seven healthy volunteers. Distension of the duodenum was done at infusion rates of 10, 25, and 50 ml/min. The pump was reversed when level 7 was reached on a visual analog scale ranging from 0 to 10. Distensions were done with and without the administration of the antimuscarinic drug butylscopolamine. The total circumferential tension ([T.sub.total]) and the passive circumferential tension ([T.sub.passive]) were determined from the distension tests without and with the administration of butylscopolamine, respectively. [T.sub.total] and [T.sub.passive] showed an exponential behavior as a function of strain (a measure of deformation). The active circumferential tension ([T.sub.active]) was computed as [T.sub.total]-[T.sub.passive] and showed a bell-shaped behavior as a function of strain. At low distension intensities, the intensity of sensation at 10 ml/min was significantly higher than that obtained at 25 and 50 ml/min. The coefficient of variation at the pain threshold for circumferential strain (average 4.34) was closer to zero compared with those for volume (8.72), pressure (31.22), and circumferential tension (31.55). This suggests that the mechanoreceptors in the gastrointestinal wall depend primarily on circumferential strain. The stimulus-response functions provided evidence for the existence of low- and high-threshold mechanoreceptors in the human duodenum. Furthermore, the data suggest that high-threshold receptors are nonadapting. cross-sectional area; distensibility; duodenum; pain; length-tension relationship

Endogenous [P.sub.i] recycling is a characteristic feature of the P homeostasis in ruminants. A pronounced salivary [P.sub.i] secretion into the rumen is balanced by a high intestinal [P.sub.i] absorption and an almost complete renal [P.sub.i] reabsorption. In monogastric animals, the major [P.sub.i] transport mechanism across the apical membrane of the enterocyte is an [Na.sup.+]-dependent transport mediated by NaPi cotransporter type IIb. In ruminants, an [Na.sup.+]-, as well as an [H.sup.+]-dependent, [P.sub.i] transport system seems to exist in the small intestines. Therefore, morphological localization, type of ionic dependence, and ability to adapt to dietary P or Ca restriction of duodenal and jejunal [P.sub.i] transport were characterized in goats. In the duodenum, there was an [H.sup.+]-dependent, [Na.sup.+]-sensitive [P.sub.i] transport system that did not belong to the NaPi type II family and was not influenced by dietary P or Ca restriction. In contrast, in the jejunum, there was an [Na.sup.+]-dependent, [H.sup.+]-sensitive [P.sub.i] transport mainly mediated by NaPi IIb. P restriction stimulated the NaPi IIb protein expression, resulting in higher [P.sub.i] transport capacity. NaPi cotransporter type IIb; proton-sensitive phosphate transport; ruminants

Betaine is used by cells to defend against changes in osmolarity. We examined relationships among betaine, osmolarity and coccidiosis. In the first experiment, chicks were fed corn-soy diets containing 0.0, 0.5 or 1.0 g/kg betaine; half were challenged with Eimeria acervulina (Cocci). Cocci decreased weight gain and feed efficiency and increased the osmolarity of the duodenal and jejunal mucosa (P < 0.01). Betaine decreased osmolarity of the duodenum (P < 0.01), especially in Cocci-challenged birds. Cocci increased the thickness (P = 0.04) of and number (P < 0.01) of leukocytes in the duodenal lamina propria especially at high betaine levels (interaction P = 0.05). Villi height was decreased by Cocci (P = 0.05) and this was ameliorated by 1.0 g/kg betaine (interaction P = 0.04). Intraepithelial leukocyte numbers were increased by Cocci (P < 0.01) especially at 0.5 and 1 g/kg betaine. Peritoneal macrophages or peripheral blood heterophils were incubated in media with an osmolarity of 200, 310, 600 or 900 mOsmol and 0.0, 0.1, 0.5 or 1.5 mmol/L betaine (4 x 4 factorial) for 6 h and then E. acervulina were added. In general, phagocytosis and NO release were decreased and interleukin (IL)-1 and IL-6 release were increased in hyperosmotic media compared with isosmotic media. Betaine (0.1 mmol/L) increased NO release by heterophils (P = 0.04) and tended to increase (P < 0.1) NO release from macrophages. The chemotaxis of monocytes toward chemotactic factors released by heterophils was increased by betaine. Increased chemotaxis of monocytes and NO release by macrophages may explain the decreased intestinal pathology but increased leukocyte numbers that were observed when betaine was fed during a Cocci infection. KEY WORDS: * broiler * betaine * immunity * coccidiosis * osmolarity

HC[O.sup.-.sub.3] secretion is the most important defense mechanism against acid injury in the duodenum. However, the identity of the transporter(s) mediating apical HC[O.sup.-.sub.3] secretion in the duodenum remains unknown. A family of anion exchangers, which include downregulated in adenoma (DRA or SLC26A3), pendrin (PDS or SLC26A4), and the putative anion transporter (PAT1 or SLC26A6) has recently been identified. DRA and pendrin mediate [Cl.sup.-]/base exchange; however, the functional identity and distribution of PAT1 (SLC26A6) is not known. In these studies, we investigated the functional identity, tissue distribution, and membrane localization of PAT1. Expression studies in Xenopus oocytes demonstrated that PAT1 functions in [Cl.sup.-]/HC[O.sup.-.sub.3] exchange mode. Tissue distribution studies indicated that the expression of PAT1 is highly abundant in the small intestine but is low in the colon, a pattern opposite that of DRA. PAT1 was also abundantly detected in stomach and heart. Immunoblot analysis studies identified PAT1 as a ~90 kDa protein in the duodenum. Immunohistochemical studies localized PAT1 to the brush border membranes of the villus cells of the duodenum. We propose that PAT1 is an apical [Cl.sup.-]/HC[O.sup.-.sub.3] exchanger in the small intestine. duodenum; bicarbonate secretion; apical [Cl.sup.-]/HC[O.sup.-.sub.3] exchange; putative anion transporter; downregulated in adenoma; chloride/formate exchanger

The orexins [orexin A (OXA) and orexin B (OXB)] are novel neuropeptides that increase food intake in rodents. The aim of this study was to determine the distribution of orexin and orexin receptors (OX1R and OX2R) in the rat duodenum and examine the effects of intravenous orexin on fasting gut motility. OXA-like immunoreactivity was round in varicose nerve fibers in myenteric and submucosal ganglia, the circular muscle, the mucosa, submucosal and myenteric neurons, and numerous endocrine cells of the mucosa. OXA neurons displayed choline acetyltransferase immunoreactivity, and a subset contained vasoactive intestinal peptide. OXA-containing endocrine cells were identified as enterochromaffin (EC) cells based on the presence of 5-hydroxytryptamine immunoreactivity. OX1R was expressed by neural elements of the gut, and EC cells expressed OX2R. OXA at 100 and 500 pmol * [kg.sup.-1] * [min.sup.-1] significantly increased the myoelectric motor complex (MMC) cycle length compared with saline. Similarly, OXB increased the MMC cycle length at 100 pmol * [kg.sup.-1] * [min.sup.-1], but there was no further effect at 500 pmol * [kg.sup.-1] * [min.sup.-1]. We postulate that orexins may affect the MMC through actions on enteric neurotransmission after being released from EC cells and/or enteric neurons. migrating motor complex; orexin receptors; enteric ganglia; enterochromaffin cells

Differences in intestinal calcium and phosphate transport between low and high bone density mice. Am J Physiol Gastrointest Liver Physiol 282: G130-G136, 2002; 10.1152/ ajpgi.00175.2001.--The purpose of this study was to determine whether there are differences in intestinal Ca and phosphate transport in mice having different peak bone densities. Intestinal transport was measured in C57BL/6 (C57, low bone density) and C3H/He (C3H, high bone density) female mice. Unidirectional (mucosal to serosal) transport of Ca was 58% higher in C3H compared with C57 mice, as measured by everted duodenal sacs. The capacity of the duodenal mucosa to take up Ca was also higher in the C3H mice. This uptake highly correlated with Ca transport across the intestine. 1,25-Dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sup.3]], which stimulates intestinal Ca absorption, markedly stimulated unidirectional Ca transport and uptake to similar levels in both strains of mice. On the other hand, unidirectional phosphate transport in C3H mice was only 36% that of C57 mice. mRNA levels of the plasma membrane Ca pump were 90% higher in the duodenum of C3H mice. There was no difference between strains in duodenal calbindin or 24-hydroxylase there was no difference in serum 1,25[(OH).sub.2][D.sub.3] levels or in renal 1[alpha]-hydroxylase mRNA levels. The combination of high intestinal Ca transport and low phosphate transport may contribute to the high peak bone density seen in the C3H relative to the C57 mouse. 1,25-dihydroxyvitamin [D.sub.3]; calbindin; intestinal 24-hydroxylase; duodenum; plasma membrane calcium pump

Research was conducted to study the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Results showed that duodenal surface mucus gel substantially restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may improve or may be a prerequisite for their effects on the gastronintestinal mucosa.

Research was conducted to test the hypothesis that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide and nitric oxide. Findings showed that luminal acid, but not bradykinin, stimulates capsazepine-sensitive receptors on capsaicin-sensitive afferent nerves of rat duodenum.

Research was conducted to examine the existence of neural connections between the duodenum and the sphincter of Oddi (SO). The objective was to test the hypothesis that a functional neural connection links the duodenum with the ganglionated plexus of the SO and that this connection could form the basis of a reflex pathway originating in the duodenal mucosa. Results demonstrate that duodenal neurons projecting to the SO provide nicotinic, fast synaptic input to SO neurons.

An in vivo anesthetized rat model was employed to study the mechanism responsible for duodenal acid-induced inhibition of gastric motility. Findings showed that multiple pathways mediate the duodenal acid-induced inhibition of gastric motility. At low rates of HCl infusion, gastric relaxation is mediated mainly by endogenous secretin, which acts through vagal afferent pathways. At higher rates of HCl infusion, gastric relaxation is mediated by endogenous secretin, cholecystokinin and possibly by the direct action of HCl on vagal afferent pathways or yet unidentified neuropathways.

The interaction between gastric volume and duodenal glucose load in the control of gastric emptying has been investigated in adult male rhesus monkeys. Duodenal glucose infusions dose dependently restricted the 10-minute emptying of different volumes of intragastric saline, while duodenal glucose right-shifted the relationship between initial gastric volume and volume emptied. These results suggest that liquid nutrient gastric emptying is a form of interaction between gastric volume and nutrient-induced duodenal feedback.

The consequences of mild hyperglycemia on the perception of, and motor responses to, duodenal distension were investigated. Paired studies were conducted in nine healthy volunteers, during euglycemia and mild hyperglycemia, in randomized fashion, utilizing a crossover design. Results showed that both the perception of, and stimulation of pyloric and duodenal pressures by, duodenal distension were enhanced by mild hyperglycemia.

The human chorionic gonadotropin (hCG) binding protein from the duodenum and pancreas was characterized and lutropin-chorionic gonadotropin receptor (LH-CGR) was localized by immunohistochemical methods utilizing antibodies directed against an epitope of LH-CGR. Findings suggest the possibility that during pregnancy hCG stimulates excessive secretion of electrolytes into the upper gastrointestinal tract, which results in vomiting during pregnancy.

The significance of gastric or duodenal origin of phase III activity was studied to elucidate the variability of the migrating motor complex (MMC). Findings showed that individual MMC cycle duration and duration of phases I, II and III are dependent on the place of origin of the preceding phase III, which explains in part the within-subject variance. Also, the origin of phase III determines the duration of phase III.

The function of calcitriol in stimulating intestinal active Ca2+ absorption during postnatal life was investigated in newborn, suckling and weaned control (Con) piglets and piglets suffering from inherited calcitrol deficiency (Def piglets). Results indicated intestinal active Ca2+ absorption during early postnatal life of pigs that involves calcitriol-independent mechanisms and that may include intact microtubule actions.

An agonist-responsive duodenocyte model was developed. The applicability of the model for defining cell-specific intracellular signaling pathways was evaluated. Primary culture models of rat and human duodenocytes that maintain agonist responsiveness for several days in culture were developed. Measurement of the changes in intracellular calcium concentration with in single cells, the presence of receptors for both cholinergic agonists and cholecystokinin on the same duodenocytes were indicated.

A study was conducted to examine the interactions between neurokinin A (NKA), vasoactive intestinal peptide (VIP), enteric nerves and prostanoids in controlling duodenal function. The abdominal cavity of Sprague-Dawley rats were prepared by a midline incision. Results indicated that increases in musocal permeability based on NK may be limited by mucosal nerves, with VIP as one of the transmitters.

A study was conducted on the involvement of gastric myoelectrical activity in intestinogastric feedback mechanisms and its relation to changes in gastric and pyloric motor activity during intraduodenal glucose infusion. The findings indicate that inhibition of gastric myoelectrical activity is one of the mechanisms by which motor activity in the gastric antrum is inhibited.

Four experiments were conducted on adult male Sprague-Dawley rats to determine whether endogenous cholecystokinin (CCK) minimizes intake by action on type A CCK receptors within the tissue perfused by the superior pancreaticoduodenal (SPD) artery in the upper gastrointestinal tract. Devazepide was found to increase sucrose intake following infusion into the SPD artery. The findings provided evidence that CCK satiety is mediated by the type A CCK receptors within the SPD arterial bed.

The relationships between distal antral and proximal duodenal load-sensitive vagal afferent activity and gastroduodenal motility in response to duodenal nutrient exposure in ketamine-xylazine-anesthetized rats were investigated. Findings showed that the proximal duodenum can discriminate its nutrient chemical contents and that gastroduodenal load-sensitive vagal afferents indirectly transduce nutrient chemical information.

The pH stat method was used in the investigation of the function of the cystic fibrosis transmembrane conductance regulator (CFTR) on the secretion of bicarbonate induced by cyclic adenylic acid across isolated duodenum segments from mice. Results reveal that the bicarbonate conductance is brought about by electrogenic and electroneutral processes brought about by bicarbonate secretion and chloride-bicarbonate exchange, respectively.

Research was conducted to investigate the functions of extrinsic innervation and plasma levels of peptide YY in mediating duodenal motility in dogs. Duodenal and ileal manometric tracings were evaluated to locate the phasic periodicity of the migrating motor complex while the colon was perfused postprandially. Results suggested separate mechanisms whereby feedback signals from colonic distension and nutrient stimulation were mediated.

The effects of neurokinin A on mucosal permeability, fluid flux, bicarbonate secretion and motility of the duodenum were investigated. Male Sprague-Dawley rats were used as experimental models along with the nicotinic receptor antagonist hexamethonium to identify the mechanisms governing the integrative responses to neurokinin A. Results showed that neurokinin A stimulated duodenal motility, bicarbonate secretion, mucosal permeability and fluid production in rats. The increased duodenal mucosal bicarbonate and motility were not linked to nicotinic transmission.

The structure and biological activity of the peptides uroguanylin and guanylin in the intestine and urine were investigated. Twelve male Sprague-Dawley rats were used as experimental models to purify bioactive uroguanylin from urine and uroguanylin and guanylin from the intestine. Results showed that the peptides exhibited biochemical and chromatographic characteristics. Messenger RNA levels for uroguanylin were higher in small intestine than in large intestine. Both uroguanylin and guanylin strongly activated receptors in T84 intestinal cells.

The impact of nutrient and hypertonic solutions infused into the duodenum on the sensory and motor functions of the stomach in relation to gastric distension was investigated. Five nonsmoking males and five nonsmoking females were subjected to infusions and distensions to assess changes in intragastric pressure during the administration of isotonic saline. Variations in sensory responses to gastric distension indicated that gastric motility changes do not explain the sensations induced by macronutrient solutions.

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in duodenal epithelial hydrogen bicarbonate secretion was analyzed in homozygous CFTR [CFTR(+/+)] and homozygous deficient [CFTR(-/-)] mice. Adenosine 3',5-cyclic monophosphate-activated duodenal epithelial hydrogen bicarbonate secretion was significantly reduced in CFTR(-/-) mice compared to CFTR(+/+) mice. Furthermore, forskolin did not affect CFTR(-/-) mice compared to CFTR(+/+) mice indicating the role of CFTR in promoting hydrogen bicarbonate secretion in the murine proximal duodenum.

The effects of proximal and distal intestinal nutrient exposure on the transition stage from the digestive to interdigestive period were analyzed in healthy human subjects. Analysis of human pancreatic and intestinal motility responses to a meal after intestinal nutrient exposure indicated the correlation between pancreatic secretory and intestinal motor responses. However, the duration and magnitude of pancreatic secretion and intestinal motor responses did not correlate with the presence of nutrients in the duodenum.

The role of cholinergic and serotonergic mechanisms on gastrointestinal motility was analyzed in normal human subjects during motilin-induced phase III antroduodenal contractions. Induction of premature antral phase III contractions in humans by the administration of exogenous motilin was inhibited by atropine indicating the role of muscarinic neural receptors in mediating gastric motility. However, atropine did not inhibit motilin-induced doudenal contractions indicating the presence of different stimulatory pathways for motilin-induced duodenal and antral contraction.

The effect of intracerebral adrenoceptor agonists on duodenal bicarbonate secretion was investigated in situ in anesthetized rats. Phenylephrine, an alpha1-selective adrenoceptor agonist, caused a rise in duodenal bicarbonate secretion. However, pretreatment with alpha1-antagonist prazosin blocked the maximal effect of phenylephrine, while hexamethonium completely abolished the effect. These results indicate that influence on duodenal bicarbonate secretion is dependent on the type adrenoceptor stimulation.

The physicochemical properties of dietary emulsions in the human stomach and duodenum during fat digestion were investigated in healthy male subjects given a coarsely emulsified test meal. Emulsified lipids in the duodenum ranged from 1-100 mumeter in size. A comparable emulsion particle size pattern was observed in the stomach contents. The stomach contents had lower triglyceride lipolysis than duodenum contents. Furthermore, the latter had higher levels of cholesterol and phospholipids. These results suggest that emulsified lipids are present in the duodenum during digestion.

The relationship between the production of duodenal ferritin H and L mRNA and iron status during postnatal development was investigated by examining ferritin subunit expression in the rat duodenum and liver during early life. Ferritin levels decreased with age in both tissue. H mRNA levels in the duodenum increased as development progressed. In contrast, L mRNA decreased significantly. There were no differences in postnatal changes in ferritin H and L mRNA in the liver. It was suggested that dietary ion contributed to the changes in ferritin in both tissues.

Measurement of the time course of absorption of duodenally injected 14C-labeled intralipid into hepatic portal circulation or system circulation shows that the satiation effect of the fats into the intestine occurs before absorption of fat into the blood and is independent of absorbed circulating fat. The plasma radioactivity increases after 30 minutes of incubation and reaches its maxima after 60-120 minutes. Calorically trivial molecules could promote endogenous satiation mechanism for regulating overconsumption of fat.

Ileal oleic acid and glucose may induce anorexia in rats by different mechanisms and these mechanisms are different from that causing anorexia induced by oleic acid and glucose in the duodenum. Researchers observed the dose-dependent effects on both ileal and duodenal infusions of oleic acid and glucose on the feeding behavior of rats. All four types of infusion reduced cumulative food intake dose-dependently. Ileal glucose and duodenal oleic acid inhibited cumulative food intake more than duodenal glucose and ileal oleic acid. Both duodenal infusions inhibited feeding frequency. Ileal glucose decreased both meal size and frequency, and ileal oleic acid decreased only meal size.

Impendancometry is a better technique for investigating Chyme transport patterns and duodenum physiology during fasting and postprandial conditions. A study of bolus transport events (BTE) in phase II of migrating motor complex cycle in 14 healthy subjects shows that short distance propulsive BTEs dominated (72%) during fasting and much of the gastric contents are continuously sent to the duodenojejunal region.

Examination of the effects of the trophic hormone gastrin and its inhibitor secretin on the modulation of ornithine decarboxylase (ODC) function in rat duodenal mucosa and IEC-6 cells reveals that gastrin elevates the expression of ODC mRNA while secretin suppresses the gastrin-stimulated ODC activity. Secretin does not influence the basal ODC activated by epidermal growth factor, refeeding, 5% dialyzed fetal bovine serum and asparagine. Inhibition of the trophic action of gastrin by secretin indicates that the growth regulating peptides on the small intestinal mucosa mediate biosynthesis of polyamines that are required for the trophic action of these hormones.

Measurement of inhibitory effects associated with varying duodenal energy load on intake enables the analysis of the influence of diet palatability during sham feeding of rats. Palatable diets exhibit higher inhibition than the less palatable ones. Duodenal energy load level influences the inhibition and intraduodenal infusion of mixed liquid diet inhibits diet intake.

In vivo studies of duodenal mucosal bicarbonate HCO3(-) secretion in anesthetized rats confirm muscarinic M1- and nicotinic receptor-mediated cholinergic influence on HCO3(-) secretion. Titration of circulating luminal perfusate quantifies the cholinergic effects. Pirenzepine- and telenzepine-catalyzed stimulation of HCO3(-) implies sympathetic ganglia-based muscarinic M1 transmission and subsequent inhibition of HCO3(-) secretion.

A similar but not identical neural process with nicotinergic receptors is involved in the enhancement of duodenal mucosal alkaline secretion (DMAS) by luminal distension and cyclooxygenase inhibition. Induction of duodenal transport probably mediates the indomethacin-induced enhancement in DMAS. This enhancement caused by indomethacin is not improved by increasing intraluminal pressure.

The acid-base movement procedure in individual, separated duodenal enterocytes was examined to investigate the functions included in the duodenal mucosal HCO3- transport. Capable duodenocytes could be separated from the duodenum of mammals. These duodenocytes possessed three acid-base transporters, an amiloride sensitive Na+-H+ exchange, dihydro-4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS) sensitive Cl--HCO3- exchange and H2DIDS-sensitive NaHCO3 cotransport, which are involved in mucosal HCO3- release.

The theory that duodenal resistance and the starting of nutrient-specific feedback supports the restriction of gastric emptying by a hyperosmolar solution was examined. The restriction of gastric emptying by hyperosmolar mannitol relied mainly on duodenal resistance, but the restrictive influence of hyperosmolar glucose more than duodenal resistance relied on nutrient-specific response of the stomach.