Involvement of glutamate and γ-amino-butyric acid receptor systems on gastric acid secretion induced by activation of κ-opioid receptors in the central nervous system in rats

摘要

Various neurotransmitters in the brain regulate gastric acid secretion. Previously, we reported that the central injection of κ-opioid receptor agonists stimulated this secretion in rats. Although the existence of κ1–κ3-opioid receptor subtypes has been proposed, the character is not defined. We investigated the interactions between κ-opioid receptor subtypes and glutamate, γ-amino-butyric acid (GABA) or 5-hydroxy tryptamine (5-HT) receptors in the rat brain.Gastric acid secretion induced by the injection of U69593 (8.41 nmol, a putative κ1-opioid receptor agonist) into the lateral cerebroventricle was completely inhibited by the central injection of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10.9 nmol, an antagonist for non-N-methyl-D-aspartate (non-NMDA) receptors) and by bicuculline infusion (222 μg kg−1 per 10 min, i.v., GABAA receptor antagonist). The secretion induced by bremazocine (8.52 nmol, a putative κ2-opioid receptor agonist) was inhibited by bicuculline infusion, but not by CNQX. The secretion induced by naloxone benzoylhydrazone (224 nmol, a putative κ3-opioid receptor agonist) was slightly and partially inhibited by CNQX and bicuculline.Treatment with CNQX and bicuculline inhibited gastric acid secretion induced by the injection of dynorphin A-(1-17) into the lateral, but not the fourth, cerebroventricle. Antagonists for NMDA, GABAB and 5-HT2/1C receptors did not inhibit the secretions by κ-opioid receptor agonists.In rat brain regions close to the lateral cerebroventricle, κ-opioid receptor systems (κ1>κ3≫κ2) are regulated by the non-NMDA type of glutamate receptor system, and κ1- and κ2-opioid receptor systems are regulated by the GABAA receptor system. The present findings show pharmacological evidence for κ-opioid receptor subtypes that regulate gastric acid secretion in the rat brain.