Neural aspects of ghrelin-induced gastroprotection against mucosal injury induced by noxious agents.
Ghrelin, identified in oxyntic mucosa has been recently implicated in the control of food intake and growth hormone (GH) release but whether this hormone can influence the gastric secretion and gastric mucosal integrity have been little studied. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by 75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy 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the area of gastric lesions was measured by planimetry, the GBF was assessed by H(2)-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. Ghrelin (5-80 microg/kg i.p. or 600-5000 ng/rat i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and I/R. These protective effects of ghrelin were accompanied by the significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20 microg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller concentrations (12.5% and 25%) produced a significant increase in plasma immunorective ghrelin levels and this effect was inhibited in rats receiving ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after its i.p. or i.c.v. administration and accompanying increase in the GBF were completely abolished by vagotomy and capsaicin-deactivation of sensory nerves. Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin denervation. We conclude that central and peripheral ghrelin exerts a potent protective and gastric secretory effects in rats exposed to ethanol and I/R, and that these actions involve vagal nerve integrity, partially depending upon afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP released from these nerves.
Brzozowski
T
T
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpbrzozo@cyf-kr.edu.pl
Konturek
P C
PC
Sliwowski
Z
Z
Drozdowicz
D
D
Kwiecien
S
S
Pawlik
M
M
Pajdo
R
R
Konturek
S J
SJ
Pawlik
W W
WW
Hahn
E G
EG
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D054439:Ghrelin / Q000097:blood / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007511:Ischemia / Q000150:complications; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013270:Stomach / Q000098:blood supply; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology* / Q000601:surgery
D005755:Gastrins; D054439:Ghrelin; D020011:Protective Agents; D011994:Recombinant Proteins; D000431:Ethanol; D002211:Capsaicin