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Background and purpose:Ghrelin, a gut-brain peptide, is considered a gastroprotective factor in gastric mucosa. We investigated the role of prostaglandins (PG) and the possible interplay between PGs and nitric oxide (NO) in ghrelin gastroprotection against ethanol (EtOH)-induced gastric lesions.Experimental approach:We examined the effects of (1) central ghrelin (4 μg per rat) injection on PGE2 accumulation in normal or EtOH–lesioned gastric mucosa, (2) pretreatment with indomethacin (10 mg kg−1, p.o.), a non-selective cyclooxygenase (COX) inhibitor, and with a selective COX-1, SC560 (5 mg kg−1, p.o.) or COX-2 inhibitor, celecoxib (3.5 mg kg−1, p.o.) on ghrelin gastroprotection against 50% EtOH (1 mL per rat)-induced gastric lesions, (3) the NO synthase inhibitor, L-NAME (70 mg kg−1, s.c), on gastric PGE2 content in ghrelin-treated rats and (4) central ghrelin on the expression of constitutive and inducible NOS and COX mRNA and on the localization of the immunoreactivity for COX-2 in the gastric mucosa exposed to EtOH.Key results:Ghrelin increased PGE2 in normal mucosa, whereas, it reversed the EtOH-induced PGE2 surge. Ghrelin had no effect on mucosal COX-1 expression but reduced the EtOH-induced increase in COX-2 expression and immunoreactivity. Indomethacin and SC560, but not celecoxib, removed ghrelin gastroprotection. L-NAME prevented the PGE2 surge induced by ghrelin and, like indomethacin, reduced EtOH-induced PGE2 increase. Ghrelin enhanced eNOS expression and reduced iNOS mRNA.Conclusions and implications:This study shows that COX-1-derived PGs are mainly involved in ghrelin gastroprotection and that the constitutive-derived NO together with PGE2 are involved in ghrelin gastroprotective activity.British Journal of Pharmacology (2008) 154, 688–697; doi:10.1038/bjp.2008.120; published online 14 April 2008 [ABSTRACT FROM AUTHOR]

Abstract: The effects of acute or long-term oral ticlopidine administration in normal rat gastric mucosa or on gastric lesions induced by ethanol 50% (EtOH, 1ml/rat, os) were examined and compared with those of acetylsalicylic acid (ASA). Ticlopidine does not affect gastric mucosal integrity either after acute (100 and 300mgkg−1) or 1-week (100mgkg−1, die) oral administration. Ticlopidine (30–300mgkg−1, os) administered 1h before EtOH dose-dependently prevented the development of gastric haemorragic lesions. When ticlopidine was administered 1h after EtOH, it significantly (p <0.05) delays gastric lesions healing. Acute ASA (50 and 100mgkg−1, os) administration causes a mild irritant activity similar to that observed after 1 week of ASA (50mgkg−1, os/die) administration. In condition of mucosal damage, ASA does not modify either the induction or the healing of EtOH-induced gastric lesions. To assess the possible involvement of endogenous nitric oxide (NO) or prostaglandins (PG) in the gastric protective activity of ticlopidine, the rats were pretreated with an inhibitor of NO-synthesis, l-NAME (70mgkg−1, s.c.) or the inhibitor of PG synthesis, indomethacin (Indo, 10mgkg−1, s.c.). Indo, but not l-NAME, was able to significantly counteract the gastroprotective activity of ticlopidine against EtOH injury. Furthermore, ticlopidine increases (47%) gastric PGE2 content in normal mucosa compared to the one detected in control rats, thus suggesting that endogenous PGs contribute to enhanced mucosal resistance by ticlopidine. These results indicate that ticlopidine exerts dual effects during the development and healing of gastric lesions induced by EtOH. [Copyright &y& Elsevier]

Abstract: This study was designed to evaluate whether or not continuous intracerebroventricular infusion of leptin (1.5μg/rat/24h, for 28 days) produced different regional response on the skeleton of growing rats. Leptin reduce the accretion of total femoral bone mineral content (BMC) and density (BMD). This effect was related to a reduction of metaphyseal femur as no changes were detected in the diaphysis. Despite the reduced accretion in the volumetric of both femur and tibia compared to controls, leptin had no significant effects on the lumbar vertebrae. Urine deoxypyrydinoline and serum osteocalcin remained more elevated in the leptin-treated group as compared to controls. The results demonstrate that long-term central infusion of leptin activates bone remodeling with a negative balance. Leptin induces distinct responses in the different structure of bone and in the axial and appendicular skeleton. [Copyright &y& Elsevier]

Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R) has been previously shown to inhibit gastric acid secretion in pylorus-ligated rats. Two isoforms of GHS-R have been identified: GHS-R1a and GHS-R1b. The present study aimed: (i) to characterise the type of GHS-R involved in the central gastric inhibitory activity of ghrelin by using des-octanoyl ghrelin, and synthetic GHS-R1a agonist (EP1572) and antagonist (D-Lys3-GHRP-6) and (ii) to investigate the relationship between ghrelin and cortistatin (CST) in the control of gastric acid secretion by using the natural neuropeptide CST-14 and the synthetic octapeptide CST-8. The specific interactions of all the compounds with GHS-R1a were determined by comparing their ability to displace labelled ghrelin or somatostatin from its receptors on rat hypothalamic membranes or on rat cardiomyocyte, respectively. Intracerebroventricular administration of 0.01 and 1 nmol/rat des-octanoyl ghrelin did not affect gastric acid secretion in pylorus-ligated rats, whereas EP1572 either i.c.v. (0.01–1 nmol/rat) or i.p. (10 and 20 nmol/kg) inhibited acid gastric secretion. Preteatment with D-Lys3GHRP-6 (3 nmol/rat, i.c.v.) was able to remove the inhibitory action of ghrelin (0.01 nmol/rat, i.c.v.) on gastric acid volume and acid output, thus indicating that the type 1a GHS-R likely mediates the gastric inhibitory action of ghrelin. This is supported by binding data showing that D-Lys3GHRP-6, but not des-octanoyl ghrelin, binds to hypothalamic GHS-R. CST-14 (1 nmol/rat, i.c.v.) did not affect either basal or ghrelin inhibition of gastric acid secretion. CST-8 (1 nmol/rat, i.c.v.) was able to counteract the gastric ghrelin response. The observation that CST-14 binds both GHR-S and somatostatin receptors, whereas CST-8 specifically displaces only ghrelin binding, indicates that CST-8 behaves as a GHS-R1a antagonist. [ABSTRACT FROM AUTHOR]

Abstract: The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin (Hexa) administration, against gastric ulcers induced by ethanol (50%, 1ml/rat/os) or Indomethacin (20mg/kg/os) were examined in conscious rats. Hexa at 1nmol/rat, icv or 10nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32% respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin-induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced ulcers was removed by the GHS-R antagonist (d-Lys3)-GRPR-6 and by the inhibitor of NO-synthase (NOS) Nω-nitro-l-arginine methyl ester. Semiquantitative RT-PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS-derived NO and the increase of constitutive-derived NO are relevant for the gastroprotection of Hexa against ethanol-induced gastric damage. [Copyright &y& Elsevier]

Discusses supercontinuum (SC) generation extending to 300 nanometer in the ultraviolet from a pure-silica holey fiber. Broad spectrum obtained by launching ultra-short pulses from an amplified Ti:sapphire laser; Extension of holey-fiber-based SC generation into the ultraviolet; Visible SC from several subsidiary cores.

We examined the possible central and peripheral effects of synthetic growth hormone secretagogues (GHS), hexarelin (Hexa) and EP 40737 (D-Thr-D-Trp (2-Me)-Ala- Trp-D-Phe-Lys-NH[sub 2] ), and of their endogenous counterpart, ghrelin, on gastric acid secretion. The compounds were administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) in conscious male rats and the volume of gastric secretion and gastric acid output were examined 3 h after pylorus ligation (Shay-test). Central Hexa, EP 40737 and ghrelin administration (from 0.1 pmol to 1 nmol/rat, i.c.v.) significantly inhibited gastric acid secretion. The maximum inhibitory effect on gastric acid output was detected at the dose of 10 pmol/rat, i.c.v. for Hexa (–51.3%), of 100 pmol/rat, i.c.v. for EP 40737 (–70%) and of 1 pmol/rat, i.c.v. for ghrelin (–60%). All peptides were less effective at the highest dose used (1 nmol/rat, i.c.v.). Hexa, EP 40737 and ghrelin injected s.c. did not modify gastric acid secretion. The inhibitory action of Hexa on gastric acid secretion seems to involve brain somatostatinergic system since Hexa (10 pmol/rat, i.c.v.) did not inhibit gastric acid secretion in rats pretreated (4 h before) with cysteamine (300 mg/kg, s.c.), a depletor of endogenous somatostatin. These results show that synthetic GHS and ghrelin exert a central long-lasting inhibitory effect on gastric acid secretion in conscious pylorus-ligated rats. The fact that very low doses of ghrelin and GHS inhibit gastric secretion, provide evidence for a tonic inhibitory role of the peptides in the central control of gastric secretory function.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A correction to the article "Evidence for a Role of the GHS-Rla Receptors in Ghrelin Inhibition of gastric Acid Secretion in the Rat," by V. Sibilia, G. Muccioli, R. Deghenghi, F. Pagani, V. de Luca, D. Rapetti, V. Locatelli and C. Netti.