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In cell line and animal models, sweet and bitter tastants induce secretion of signaling peptides (e.g., glucagon-like peptide-I and cholecystokinin) and slow gastric emptying (GE). Whether human GE and appetite responses are regulated by the sweetness or bitterness per se of ingested food is, however, unknown. We aimed to determine whether intragastric infusion of 'equisweet' (Stud), A) or 'equibitter' (Study B) solutions slow GE to the same extent, and whether a glucose solution made sweeter by the addition of saccharin will slow GE more potently than glucose alone. Healthy nonobese subjects were studied in a single-blind, randomized fashion. Subjects received 500-ml intragastric infusions of predetermined equisweet solutions of glucose (560 mosmol/kg[H.sub.2]O), fructose (290 mosmol/kg[H.sub.2]O), aspartame (200 mg), and saccharin (50 mg); twice as sweet glucose + saccharin, water (volumetric control) (Study A); or equibitter solutions of quinine (0.198 mM), naringin (1 mM), or water (Study B). GE was evaluated using a [[sup.13]C]acetate breath test, and hunger and fullness were scored using visual analog scales. In Study A, equisweet solutions did not empty similarly. Fructose, aspartame, and saccharin did not slow GE compared with water, but glucose did (P < 0.05). There was no additional effect of the sweeter glucose + saccharin solution (P > 0.05, compared with glucose alone). In Study B, neither bitter tastant slowed GE compared with water. None of the solutions modulated perceptions of hunger or fullness. We conclude that, in humans, the presence of sweetness and bitterness taste per se in ingested solutions does not appear to signal to influence GE or appetite perceptions. taste; gastrointestinal tract; bitter; sweet

Pancreatic duct epithelium secretes a HC[O.sub.3.sup.-]-rich fluid by a mechanism dependent on cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane. However, the exact role of CFTR remains unclear. One possibility is that the HC[O.sub.3.sup.-] permeability of CFTR provides a pathway for apical HC[O.sub.3.sup.-] efflux during maximal secretion. We have therefore attempted to measure electrodiffusive fluxes of HC[O.sub.3.sup.-] induced by changes in membrane potential across the apical membrane of interlobular ducts isolated from the guinea pig pancreas. This was done by recording the changes in intracellular pH ([pH.sub.i]) that occurred in luminally perfused ducts when membrane potential was altered by manipulation of bath [K.sup.+] concentration. Apical HC[O.sub.3.sup.-] fluxes activated by cyclic AMP were independent of [Cl.sup.-] and luminal [Na.sup.+], and substantially inhibited by the CFTR blocker, [CFTR.sub.inh]-172. Furthermore, comparable HC[O.sub.3.sup.-] fluxes observed in ducts isolated from wild-type mice were absent in ducts from cystic fibrosis ([DELTA]F) mice. To estimate the HC[O.sub.3.sup.-] permeability of the apical membrane under physiological conditions, guinea pig ducts were luminally perfused with a solution containing 195 mM HC[O.sub.3.sup.-] and 24 mM [Cl.sup.-] in the presence of 5% C[O.sub.2]. From the changes in [pH.sub.i], membrane potential, and buffering capacity, the flux and electrochemical gradient of HC[O.sub.3.sup.-] across the apical membrane were determined and used to calculate the HC[O.sub.3.sup.-] permeability. Our estimate of ~0.1 [micro]m [sec.sup.-1] for the apical HC[O.sub.3.sup.-] permeability of guinea pig duct cells under these conditions is close to the value required to account for observed rates of HC[O.sub.3.sup.-] secretion. This suggests that CFTR functions as a HC[O.sub.3.sup.-] channel in pancreatic duct cells, and that it provides a significant pathway for HC[O.sub.3.sup.-] transport across the apical membrane.

An integrate picture of ductal bicarbonate secretion along with a critical review on its development is reviewed. The secretion of moderate concentrations of HCO3(super -) could be explained by the parallel activity of a Cl(super -) and HCO3(super -) exchanger and a Cl(super -) conductance, either the cystic fibrosis transmembrane conductance regulator (CFTR) or a Ca(super 2+)-activated Cl(super -) channel (CaCC).

Enteroendocrine cells have a critical role in regulation of appetite and energy balance. I-cells are a subtype of enteroendocrine cells localized in duodenum that release cholecystokinin in response to ingested fat and amino- acids. Despite their potentially pivotal role in nutrient sensing and feeding behaviour, native I-cells have previously been difficult to isolate and study. Here we describe a robust protocol for the isolation and characterization of native duodenal I-cells and additionally, using semi-quantitative RT-PCR we determined that mouse duodenal I-cells contain mRNA transcripts encoding key fatty acid and endocannabinoid receptors including the long chain fatty acid receptors GPR40/FFAR1, GPR120/O3FAR1; short chain fatty acid receptors GPR41/FFAR3 and GPR43/FFAR2; the oleoylethanolamide receptor GPR119 and the classic endocannabinoid receptor CB1. These data suggest that I-cells sense a wide range of gut lumen nutrients and also have the capacity to respond to signals of fatty-acid derivatives or endocannabinoid peptides. [ABSTRACT FROM AUTHOR]

Abstract: Specific Ca2+ homeostatic system appeared very early in the history of the cell, as a survival system preventing Ca2+-mediated cell damage. This homeostatic system produced a steep (∼20,000 times) concentration gradient between extracellular and intracellular compartments, which has both survival importance (even relatively short increases in cytosolic Ca2+ concentrations higher then 100nM are incompatible with life) and signalling function. Evolution utilised this gradient together with an ability of Ca2+ to interact with many biological molecules to create the most widespread and versatile signalling system, controlling the majority of cellular processes and executing complex routines of intercellular communications. [Copyright &y& Elsevier]

Human pancreatic ducts secrete a bicarbonate-rich fluid but our knowledge of the secretory process is based mainly on studies of animal models. Our aim was to determine whether the HCO3- transport mechanisms in a human ductal cell line are similar to those previously identified in guinea-pig pancreatic ducts. Intracellular pH was measured by microfluorometry in Capan-1 cell monolayers grown on permeable filters and loaded with BCECF. Epithelial polarization was assessed by immunolocalization of occludin. Expression of mRNA for key electrolyte transporters and receptors was evaluated by RT-PCR. Capan-1 cells grown on permeable supports formed confluent, polarized monolayers with well developed tight junctions. The recovery of pHi from an acid load, induced by a short NH4+ pulse, was mediated by Na+-dependent transporters located exclusively at the basolateral membrane. One was independent of HCO3- and blocked by EIPA (probably NHE1) while the other was HCO3--dependent and blocked by H2DIDS (probably pNBC1). Changes in pHi following blockade of basolateral HCO3- accumulation confirmed that the cells achieve vectorial HCO3- secretion. Dose-dependent increases in HCO3- secretion were observed in response to stimulation of both secretin and VPAC receptors. ATP and UTP applied to the apical membrane stimulated HCO3- secretion but were inhibitory when applied to the basolateral membrane. HCO3- secretion in guinea-pig ducts and Capan-1 cell monolayers share many common features, suggesting that the latter is an excellent model for studies of human pancreatic HCO3- secretion. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]