High affinity [3H]ethylketazocine binding: evidence for specific kappa receptors

A study has been made of the inactivation of mu(mu) ([3H]-dihydromorphine), delta (delta) ([3H](D-ala2-D-leu5)enkephalin) and kappa (kappa) ([3H]ethylketazocine) opiate receptor binding sites by N-ethylmaleimide (NEM) and it was observed that in contrast to mu and delta sites, the kappa sites of rat brain membrane preparations were resistant to low concentrations of N-ethylmaleimide. Furthermore, this kappa site was selectively protected, from inactivation with high concentrations of N-ethylmaleimide, by the kappa agonists ethylketazocine and (-)-alpha-(1R,5R,9R)-5,9-dimethyl-2-(L-tetrahydrofurfuryl)-2'-hydroxy-6,7-benzo morphan (MR-2034) but not by morphine or (D-ala2-D-leu5)-enkephalin. These studies suggest that a unique kappa receptor is present in the rat CNS.