KAPPA-OPIOID RECEPTOR-MEDIATED SUPPRESSION OF VOLTAGE-ACTIVATED POTASSIUM CURRENT IN A CATECHOLAMINERGIC NEURONAL CELL-LINE

Opioid sensitivity of a catecholaminergic cell line (CATH.a) of brains tem origin was examined using whole-cell voltage-clamp techniques. Mor phine produced a preferential and concentration-dependent decrease of the amplitude of voltage-activated potassium current, I-K (ED(50) = si milar to 4 mu M, maximum inhibition 52%, n = 33). The mu-selective opi ate agonist [D-Ala(2), MePhe, Gly-ol(5)] enkephalin (2-20 mu M; n = 6) and the delta-selective agonist [D-Pen(2), D-Pen(5)] enkephalin (2-20 mu M; n = 7) produced no effect. However, the kappa-selective agonist -N-(2-[1-pyrrolidinyl]cyclohexyl)benzene-acetamide reduced I-K in a c oncentration-dependent manner (EC(50) = 2.3 mu M, maximum inhibition 4 4%, n = 40). The kappa receptor antagonist nor-binaltorphimine (10 nM) blocked the effect of either morphine (10 mu M, n = 6) or U50,488 (10 mu M, n = 7). Kappa agonist-mediated I-K reduction was prevented by i ntracellular dialysis with an inactive form of guanosine diphosphate, guanosine 5'-O-(2-thio)diphosphate (100-200 mu M; n = 10) but was unch anged by incubation with pertussis toxin (500 ng/ml, 24-48 h, n = 10). These results suggest that opioid suppression of I-K is mediated by k appa-opioid receptors coupled to a pertussis toxin-insensitive G-prote in.