Involvement of glutamate and gamma-amino-butyric acid receptor systems on gastric acid secretion induced by activation of kappa-opioid receptors in the central nervous system in rats.
1. Various neurotransmitters in the brain regulate gastric acid secretion. Previously, we reported that the central injection of kappa-opioid receptor agonists stimulated this secretion in rats. Although the existence of kappa(1)-kappa(3)-opioid receptor subtypes has been proposed, the character is not defined. We investigated the interactions between kappa-opioid receptor subtypes and glutamate, gamma-amino-butyric acid (GABA) or 5-hydroxy tryptamine (5-HT) receptors in the rat brain. 2. Gastric acid secretion induced by the injection of U69593 (8.41 nmol, a putative kappa(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 micro g kg(-1) per 10 min, i.v., GABA(A) receptor antagonist). The secretion induced by bremazocine (8.52 nmol, a putative kappa(2)-opioid receptor agonist) was inhibited by bicuculline infusion, but not by CNQX. The secretion induced by naloxone benzoylhydrazone (224 nmol, a putative kappa(3)-opioid receptor agonist) was slightly and partially inhibited by CNQX and bicuculline. 3. 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 kappa-opioid receptor agonists. 4. In rat brain regions close to the lateral cerebroventricle, kappa-opioid receptor systems (kappa(1)>kappa(3)>>kappa(2)) are regulated by the non-NMDA type of glutamate receptor system, and kappa(1)- and kappa(2)-opioid receptor systems are regulated by the GABA(A) receptor system. The present findings show pharmacological evidence for kappa-opioid receptor subtypes that regulate gastric acid secretion in the rat brain.
Minowa
Sachie
S
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
Ishihara
Satomi
S
Tsuchiya
Shizuko
S
Horie
Syunji
S
Watanabe
Kazuo
K
Murayama
Toshihiko
T
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D044482:Benzeneacetamides / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D004399:Dynorphins / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism / Q000502:physiology*; D007276:Injections, Intraventricular; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010477:Perfusion / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate / Q000187:drug effects*; D018092:Kainic Acid Receptors / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa / Q000008:administration & dosage / Q000819:agonists* / Q000502:physiology*; D011985:Receptors, Serotonin; D013270:Stomach / Q000187:drug effects / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001418:Baclofen; D044482:Benzeneacetamides; D001575:Benzomorphans; D001640:Bicuculline; D004399:Dynorphins; D007650:Ketanserin; D010879:Piperazines; D011759:Pyrrolidines; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D011985:Receptors, Serotonin; D005680:gamma-Aminobutyric Acid; C052329:phaclofen; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C027248:bremazocine; C045444:U 69593