INHIBITORY EFFECTS OF NACL AND GUANYL-5'YL-IMIDODIPHOSPHATE (GPPNHP) ON [H-3] NALOXONE BINDING TO KAPPA-OPIOID RECEPTORS IN GUINEA-PIG CEREBELLUM

Studies were performed to characterize the opioid receptors in guinea pig brain using the radiolabeled opioid antagonists, [H-3]naloxone and [H-3]diprenorphine and the kappa-agonist [H-3]U-69593. The binding of [H-3]U-69593 to guinea pig cerebellar membranes was reduced by NaCl, guanyl-5'yl-imidodiphosphate (GppNHp) and NaCl + GppNHp, and [H-3]nalo xone binding to cerebellar membranes was also reduced by NaCl and GppN Hp. In the guinea pig cerebral cortex and striatum and the rat cerebel lum, [H-3]naloxone binding was not affected significantly by GppNHp in the presence or absence of 100 nm [D-Ala2,N-Me-Phe4,Gly5-ol]enkephali n (DAMGO) and [D-Ala2, D-Leu5]enkephalin (DADLE). Guinea pig cerebella r [H-3]diprenorphine binding was not affected by NaCl, GppNHp or NaCl + GppNHp. Furthermore, [H-3]naloxone binding was reduced after pretrea ting cerebellar membranes with N-ethylmaleimide (NEM), which also atte nuated GppNHp-induced inhibition of cerebellar [H-3]naloxone binding. These results suggest that the properties of [H-3]naloxone binding in guinea pig cerebellum differ from those in other brain regions and rat cerebellum, and that the interaction of [H-3]naloxone and [H-3]U-6959 3, but not [H-3]diprenorphine, with guinea pig cerebellar opioid recep tors is associated with a G-protein.