Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence

Abstract

Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H2-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5-80 microg/kg i.p. or 0.6-5 microg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves.

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle

“…On the basis of a C-terminal Gly-Lys motif, amidation of obestatin was assumed and verified as a prerequisite for biological activity [162]. Furthermore, the mass spectrometric data indicated that this peptide may be processed to a 13 amino acid peptide, obestatin (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Further information is required to establish exactly how obestatin (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) is formed, although, a recent study indicates that this isoform is indeed biologically active [62].…”

“…Indeed, a gastroprotective effect has been demonstrated in various models, which seems to depend mainly on vagal activity, sensory nerves and hyperaemia mediated by nitric oxide synthase-nitric oxide (NOS-NO) and cyclooxygenase-prostaglandin systems [15,16]. The protective effect has also been demonstrated in experimental colitis [57].…”

The Role of Capsaicin-Sensitive Afferent Nerves in Gastric Mucosal Protection Initiated Centrally or Peripherally under Experimental Conditions

“…amylin, adrenomedullin, neurotensin, opioid peptides, melatonin, ghrelin, leptin, as well as cannabinoids were shown to initiate gastroprotective effect given centrally (i.c.v., i.c. or DMNV), mostly by a vagal dependent mechanism [139][140][141][142] (see reviews: [4,127,138,143,144]). …”

Pathophysiology of Gastric Ulcer Development and Healing: Molecular Mechanisms and Novel Therapeutic Options

“…Other hormone mediators, including gastrin-17, cholecystokinin, thyrotropin-releasing hormone, bombesin, EGF, peptide YY and neurokinin A, play significant roles in the regulation of gastric protective mechanisms, which can be blunted by afferent nerve ablation, CGRP receptor blockade, and inhibition of NO synthase (Peskar, 2001;Moszik et al, 2001). Ghrelin, a hormone peptide produced by gastric A-like cells in rodents and P/D1 cells in humans, is involved in the regulation of growth hormone secretion and appetite stimulation (Brzozowski et al, 2005b). Moreover, it is also able to exert significant protective effects at gastric level, including the enhancement of mucosal blood flow via stimulation of NO and CGRP release from sensory afferent nerves (Brzozowski et al, 2005b).…”