[Cholecystokinin receptors involved in the central and peripheral nervous control mechanisms in gastric acid secretion].
Cholecystokinin (CCK) has a unique pharmacological profile as a "brain-gut peptide hormone", and recent development of specific non-peptide antagonists prompted us to investigate the role of the receptors of this peptide in nervous control mechanisms of gastric acid secretion. CCK-8 induced a distinctive acid secretory response after intracerebroventricular (i.c.v.) administration, as well as after intravenous infusion in the perfused stomach preparation in rats. L364718, a CCKB-receptor antagonist, had an inhibitory effect against CCK-8 when applied i.c.v., while L365260, a CCKB-receptor antagonist, had no influence, suggesting the apparent dominant control of CCKA receptors in the central nervous system on gastric acid secretion. However, L364718 caused remarkable potentiation in the acid secretory response to the intravenous CCK-8 infusion, and L365260 significantly inhibited the CCK-8-stimulated acid secretion. The potentiation of the acid secretory response to CCK-8 by the CCKA antagonist was completely blocked by vagotomy or atropine, as well as hexamethonium. Thus it was suggested that a vagal control mechanism was involved in the potentiation. Denervation of capsaicin-sensitive primary afferent nerve by repeated capsaicin injection also decreased the potentiated response to CCKA antagonist. This seems to suggest the involvement of the vago-vagal reflex in the control of gastric acid secretion by endogenous CCK. Ketanserin, a serotonin 5-HT2/1C-receptor antagonist, showed a distinctive inhibition of acid secretion induced by CCK-8 (i.c.v.), suggesting the involvement of serotonergic control of acid secretion in the CCK-8 action. Current developments in the research in this field were briefly reviewed in relation to our findings.
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
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Watanabe
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Yano
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Mitani
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002490:Central Nervous System / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D017933:Peripheral Nervous System / Q000502:physiology; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology / Q000502:physiology
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D012844:Sincalide