Exogenous and endogenous ghrelin in gastroprotection against stress-induced gastric damage.
Ghrelin, identified in the gastric mucosa has been involved in control of food intake and growth hormone (GH) release but little is known about its influence on gastric secretion and mucosal integrity. The effects of ghrelin on gastric secretion, plasma gastrin and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) were determined. Exogenous ghrelin (5, 10, 20, 40 and 80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS and this was accompanied by the significant rise in plasma ghrelin level, gastric mucosal blood flow (GBF) and luminal NO concentrations. Ghrelin-induced protection was abolished by vagotomy and attenuated by suppression of COX, deactivation of afferent nerves with neurotoxic dose of capsaicin or CGRP(8-37) and by inhibition of NOS with L-NNA but not influenced by medullectomy and administration of 6-hydroxydopamine. We conclude that ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol and WRS, and these effects depend upon vagal activity, sensory nerves and hyperemia mediated by NOS-NO and COX-PG systems.
Brzozowski
T
T
Department of Physiology, Jagiellonian University Medical College, 16, Grzegorzecka Street, 31-531 Cracow, Poland. mpbrzozo@cyf-kr.edu.pl
Konturek
P C
PC
Konturek
S J
SJ
Kwiecień
S
S
Drozdowicz
D
D
Bielanski
W
W
Pajdo
R
R
Ptak
A
A
Nikiforuk
A
A
Pawlik
W W
WW
Hahn
E G
EG
D018663:Adrenergic Agents / Q000008:administration & dosage; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D051545:Cyclooxygenase 1; D000431:Ethanol / Q000633:toxicity*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply* / Q000473:pathology; D005755:Gastrins / Q000097:blood; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008916:Miotics / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016627:Oxidopamine / Q000008:administration & dosage; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
D018663:Adrenergic Agents; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002492:Central Nervous System Depressants; D005755:Gastrins; D054439:Ghrelin; D007527:Isoenzymes; D008565:Membrane Proteins; D008916:Miotics; D010446:Peptide Fragments; D036361:Peptide Hormones; C058636:calcitonin gene-related peptide (8-37); D009569:Nitric Oxide; D000431:Ethanol; D016627:Oxidopamine; D013006:Growth Hormone; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin