ANTAGONISM BY GLIBENCLAMIDE OF THE EFFECT OF MORPHINE IN HIPPOCAMPAL PREPARATIONS

We previously showed that morphine lowered the affinity of Ca2+ antago nist binding and subsequently enhanced field potentials in hippocampal preparations. In the present study, the effect of various K+ channel antagonists on these actions of morphine was studied. Higher K(d) valu e of [H-3]nitrendipine binding was obtained for membranes prepared fro m slices treated with morphine. Concomitant treatment of slices with m orphine and tetramethylammonium (TMA) or glibenclamide attenuated the effect of morphine. Apamin and mast cell-degranulating (MCD) peptide w ere without effect on morphine-induced change in [H-3]nitrendipine bin ding. In those experiments, no change in concentration of binding site s was observed. Glibenclamide reduced the morphine enhancement of fiel d potentials. These results suggested the regulation of Ca2+ channels by morphine through K+ channel opening.