Evidence for a Central Inhibitory Role of Growth Hormone Secretagogues and Ghrelin on Gastric Acid Secretion in Conscious Rats

Abstract

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-NH₂), 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.

Helicobacter pylori has no effect on plasma ghrelin levels

“…Ghrelin also stimulates gastric motility and acid secretion in rats (13,14). A recent study has shown that central ghrelin administration decreases gastric acid secretion, but peripheral administration does not modify gastric acid secretion in rats (15). Peripheral ghrelin administration also has no effect on gastric emptying in humans (12).…”

Ghrelin regulates proliferation and differentiation of osteoblastic cells

“…Ghrelin was shown to be a 28 amino acid peptide bearing the unique acylation on the Ser 3 residue (Kojima et al 1999(Kojima et al , 2001. Ghrelin, as well as many GHS, also participates in the regulation of energy homeostasis (Inui 2001), cardiovascular (Bodart et al 1999, Locatelli et al 1999) and gastric functions (Sibilia et al 2002). However, the widespread expression of the genes encoding ghrelin and its cognate receptor in a variety of tissues including adrenals, prostate, thymus, hypothalamus, hippocampus and bone (Komatsu et al 2000, Broglio et al 2002, Guanapavan et al 2002 strongly supports a potential for multiple biological activities of ghrelin (van der Lely et al 2004).…”

Distribution of ghrelin-positive mast cells in rat stomach

“…This role of ghrelin is important because during fasting, increased ghrelin serum level and decreased acid secretion protect the gastric mucosa. Based on assumptions of Sibilia et al [62], we suggested that ghrelin-positive MCs in the gastric smooth muscle and near the proper gastric glands of the rat stomach could assist in regulation of stomach motility and acid secretion. Thus, we suggested that similarly to histamine and eicosanoids, ghrelin is another MC mediator participating in the regulation of smooth muscle contraction [45,46].…”

“…Role of ghrelin in the stomach is controversial. Several researchers reported that ghrelin can influence gastric activity, especially its motility and acid secretion [60][61][62][63]. According to Masuda et al [58], ghrelin increases stomach motility and acid secretion while Sibilia et al [61] reported that ghrelin inhibits acid secretion.…”