Role of central oxytocin in the inhibition by endotoxin of distension-stimulated gastric acid secretion.
The gastric acid hyposecretory state associated with endotoxemia is mediated by a nervous reflex involving the central nervous system. The aim of the present study was to analyse the central effects of different peptides on distension-stimulated gastric acid secretion and the endogenous role of such peptides on the hyposecretory effects of endotoxin. The effect of an intracisternal (i.c.) administration of oxytocin, vasopressin, corticotropin releasing factor (CRF), bombesin, somatostatin and the opioid receptor agonist BW443C or an intravenous (i.v.) injection of a small dose of endotoxin on distension-stimulated gastric acid secretion was studied in the continuously perfused stomach of anaesthetised rats. In some animals, specific receptor antagonists for oxytocin (Compound VI [d(CH2)5, Tyr(Me)2, Thr4, Tyr-NH2(9)]-OVT, 0.01-1 microg/rat), vasopressin (des-Gly9-[beta-Mercapto-beta,beta-cyclopentamethylene-propiony l1, O-Et-Tyr2, Val4, Arg8]-VP, 20 microg/rat), CRF (alpha-helical CRF [9-41], 50 microg/rat) or bombesin (D-Phe12-Bombesin, 20 microg/rat) were administered i.c. before endotoxin. Distension-stimulated acid secretion was significantly inhibited by central oxytocin (0.2, 2 or 4 nmol/rat, 45+/-16%, 69+/-10% and 79+/-5% reduction, respectively), CRF (0.5, 1 or 2 nmol/rat, 52.2+/-15.6%, 74.3+/-9.1% and 93.2+/-1.6% reduction, respectively) and bombesin (2 nmol/rat, 79.1+/-5.8% reduction). The hyposecretory effect induced by endotoxin (5 microg/kg, 60.2+/-2.3% reduction) was reversed in a dose-dependent manner by pretreatment with the oxytocin receptor antagonist (0.01, 0.1 and 1 microg/rat, 65.2+/-14.4%, 88.0+/-22.5% and 112.4+/-25.2% of control response, respectively) while the vasopressin (20 microg/rat), CRF (50 microg/rat) or bombesin (20 microg/rat) receptor antagonists had no effect. The present results support a role for the endogenous release and action in the central nervous system of oxytocin in the inhibitory effect of endotoxin on gastric acid secretion.
Calatayud
S
S
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Quintana
E
E
Esplugues
J
J
Barrachina
M D
MD
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001839:Bombesin / Q000008:administration & dosage; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D004731:Endotoxins; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D013271:Gastric Dilatation / Q000139:chemically induced / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006728:Hormones / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage; D010121:Oxytocin / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000008:administration & dosage; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014667:Vasopressins / Q000008:administration & dosage
D018663:Adrenergic Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D004731:Endotoxins; D006728:Hormones; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018004:Receptors, Bombesin; D018019:Receptors, Corticotropin-Releasing Hormone; D018045:Receptors, Oxytocin; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D010121:Oxytocin; D013004:Somatostatin; C055303:BW 443C; D003346:Corticotropin-Releasing Hormone; D001839:Bombesin