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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
Author(s) -
Minowa Sachie,
Ishihara Satomi,
Tsuchiya Shizuko,
Horie Syunji,
Watanabe Kazuo,
Murayama Toshihiko
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705082
Subject(s) - bicuculline , cnqx , κ opioid receptor , chemistry , endocrinology , medicine , agonist , dynorphin , (+) naloxone , opioid receptor , receptor antagonist , receptor , pharmacology , opioid , nmda receptor , ampa receptor , biology , opioid peptide , gabaa receptor , biochemistry , antagonist
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 κ 1 – κ 3 ‐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 κ 1 ‐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 μ g kg −1 per 10 min, i.v., GABA A receptor antagonist). The secretion induced by bremazocine (8.52 nmol, a putative κ 2 ‐opioid receptor agonist) was inhibited by bicuculline infusion, but not by CNQX. The secretion induced by naloxone benzoylhydrazone (224 nmol, a putative κ 3 ‐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, GABA B and 5‐HT 2/1C receptors did not inhibit the secretions by κ ‐opioid receptor agonists. In rat brain regions close to the lateral cerebroventricle, κ ‐opioid receptor systems ( κ 1 > κ 3 ≫ κ 2 ) are regulated by the non‐NMDA type of glutamate receptor system, and κ 1 ‐ and κ 2 ‐opioid receptor systems are regulated by the GABA A receptor system. The present findings show pharmacological evidence for κ ‐opioid receptor subtypes that regulate gastric acid secretion in the rat brain.British Journal of Pharmacology (2003) 138 , 1049–1058. doi: 10.1038/sj.bjp.0705082