Pathways mediating CRF-induced inhibition of gastric acid secretion in rats.
The pathways involved in mediating the central nervous system actions of corticotropin-releasing factor (CRF) on gastric acid secretion were examined in conscious rats. CRF (0.1-2.0 nmol) given cerebroventricularly inhibited gastric acid secretion stimulated by pentagastrin (P less than 0.01). This effect was abolished by cerebroventricular but not intravenous administration of a specific CRF receptor antagonist, alpha-helical CRF-(9-41). Ganglionic blockade with chlorisondamine chloride, noradrenergic blockade with bretylium, or adrenalectomy abolished the gastric inhibitory action of CRF whereas truncal vagotomy or opiate blockade with naloxone did not. A vasopressin receptor antagonist significantly inhibited but did not abolish the gastric inhibitory action of CRF. An intravenous infusion of epinephrine that mimicked the epinephrine plasma concentrations which were observed after cerebroventricular administration of CRF did not alter pentagastrin-stimulated gastric acid secretion. These results indicate that CRF acts within the central nervous system to inhibit gastric acid secretion by a specific receptor-mediated event. Inhibition of gastric acid secretion by CRF in conscious rats is mediated by efferent fibers of the sympathetic nervous system and in part by a vasopressin-dependent pathway but not by the parasympathetic nervous system, adrenal epinephrine release, or opiate-sensitive pathways.
Department of Medicine, University of Hamburg, Federal Republic of Germany.
G
G
Drüge
A
A
Raedler
H
H
Greten
H J
HJ
Lenz
D000315:Adrenalectomy; D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology; D002714:Chlorisondamine / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D005744:Gastric Acid / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014628:Vagotomy
D001949:Bretylium Compounds; D010446:Peptide Fragments; D009270:Naloxone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D010418:Pentagastrin; D002714:Chlorisondamine; C045166:bretylium