RT Journal Article
SR Electronic
T1 GR89,696 Is a <em>Kappa</em>-2 Opioid Receptor Agonist and a <em>Kappa</em>-1 Opioid Receptor Antagonist in the Guinea Pig Hippocampus
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1342
OP 1349
VO 283
IS 3
A1 Caudle, Robert M.
A1 Mannes, Andrew J.
A1 Iadarola, Michael J.
YR 1997
UL http://jpet.aspetjournals.org/content/283/3/1342.abstract
AB Receptor binding studies and electrophysiological studies demonstrated the existence of at least two kappa opioid receptors, which have been designated kappa-1 andkappa-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, thekappa opioid GR89,696 was tested in the guinea pig hippocampal slice preparation for kappa-1versuskappa-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. The American Society for Pharmacology and Experimental Therapeutics