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.
ABSTRACT 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.
Article: GR89,696 is a kappa-2 opioid receptor agonist and a kappa-1 opioid receptor antagonist in the guinea pig hippocampus.[show abstract] [hide abstract]
ABSTRACT: Receptor binding studies and electrophysiological studies demonstrated the existence of at least two kappa opioid receptors, which have been designated kappa-1 and kappa-2. Several agonists and antagonists are selective for the kappa-1 receptor whereas no known ligands are selective for the kappa-2 receptor. In this study, the kappa opioid GR89,696 was tested in the guinea pig hippocampal slice preparation for kappa-1 versus kappa-2 activity. The perforant path-evoked population spike in the dentate was use to evaluate activity at the kappa-1 receptor, and the Schaffer collateral-evoked N-methyl-D-aspartate (NMDA) receptor-mediated synaptic current in CA3 pyramidal cells was used to measure kappa-2 receptor activation. GR89,696 had no effect on the perforant path-evoked dentate population spike; however, it did reverse the effects of the selective kappa-1 agonist U69,593 when co-perfused over the slices. In the CA3, GR89,696 inhibited the NMDA receptor-mediated synaptic current. The inhibition was antagonized by naloxone. The EC50 for GR89,696 on the NMDA current was 41.7 nM (95% CL, 7.0-248 nM). These findings indicate that GR89,696 is an agonist for kappa-2 opioid receptors and an antagonist at kappa-1 receptors in the guinea pig hippocampus.Journal of Pharmacology and Experimental Therapeutics 01/1998; 283(3):1342-9. · 3.83 Impact Factor