Peptidergic and cholinergic neurons and mediators in peptone-induced gastroprotection: role of cyclooxygenase-2.
This study investigates the neural pathways, mediators, and cyclooxygenase isoenzymes involved in the gastroprotection conferred by peptone in rats. Intragastric perfusion with 8% peptone protected against gross and histological damage induced by subsequent perfusion with 50% ethanol. The gastroprotective effect of peptone was near maximally inhibited by gastrin immunoneutralization, inactivation of capsaicin-sensitive afferent neurons, calcitonin gene-related peptide (CGRP) immunoneutralization, blockade of gastrin receptors, CGRP, bombesin/gastrin-releasing peptide (GRP), or somatostatin receptors, and by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester and was partially (46%) counteracted by atropine. Indomethacin and the selective cyclooxygenase-2 inhibitors NS-398 and L-745,337 dose dependently (50% inhibitory dose, 4.2, 0.8, and 1.5 mg/kg, respectively) attenuated the peptone-induced protection. Dexamethasone was ineffective. These results indicate that protective effects of peptone involve endogenous gastrin and possibly somatostatin and are mediated by capsaicin-sensitive afferent, cholinergic, and bombesin/GRP neurons. CGRP, NO, and prostaglandins participate as essential mediators. The study provides evidence that prostaglandins derived from a constitutive cyclooxygenase-2 contribute to mucosal defense in the presence of ulcerogens and thus participate in homeostatic functions of the stomach.
Ehrlich
K
K
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, Germany.
Plate
S
S
Stroff
T
T
Gretzer
B
B
Respondek
M
M
Peskar
B M
BM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001839:Bombesin / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D051546:Cyclooxygenase 2; D005753:Gastric Mucosa / Q000098:blood supply; D005755:Gastrins / Q000502:physiology; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D010461:Peptones / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013004:Somatostatin / Q000502:physiology; D013270:Stomach / Q000187:drug effects*
D005755:Gastrins; D007527:Isoenzymes; D010455:Peptides; D010461:Peptones; D013004:Somatostatin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015740:Calcitonin Gene-Related Peptide; D001839:Bombesin