Differential effects of diazoxide, cromakalim and pinacidil on adrenergic neurotransmission and 86Rb+ efflux in rat brain cortical slices

Abstract

The effects of diazoxide, cromakalim and pinacidil on depolarization-evoked tritium overflow from the rat brain cortical slices preloaded with [3H]noradrenaline were studied. Diazoxide inhibited both transmural nerve stimulation (TNS)- and 25 mM K(+)-evoked tritium overflows more potently than cromakalim. Diazoxide effects were only partially antagonized and cromakalim ones were totally reversed by 1 microM glibenclamide. Diazoxide, but not cromakalim, reduced the 45 mM K(+)-evoked tritium overflow, which was not antagonized by glibenclamide. Both diazoxide and cromakalim stimulated 86Rb+ efflux to a similar extent, the effects being completely abolished by glibenclamide. Glibenclamide (> or = 3 microM) by itself enhanced the TNS-evoked tritium overflow. Pinacidil increased both TNS- and K+ (25 and 45 mM)-evoked tritium overflows with little effect on 86Rb+ efflux. Pinacidil-induced increase in the TNS-evoked tritium overflow was still observed in the presence of cocaine or hydrocortisone. Pinacidil failed to affect the inhibitory action of xylazine on the TNS-evoked tritium overflow, whereas phentolamine attenuated it. These results indicate that ATP-sensitive K+ channels are present in the adrenergic nerve endings of rat brain. These channels seem to be pharmacologically different from those reported for vascular smooth muscles and pancreatic beta-cells.