Differential effects of diazoxide, cromakalim and pinacidil on adrenergic neurotransmission and 86Rb+ efflux in rat brain cortical slices.
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.
Takata
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Shimada
F
F
Kato
H
H
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology*; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000378:metabolism*
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D020110:Pinacidil; D003042:Cocaine; D003981:Diazoxide; D005905:Glyburide; D006854:Hydrocortisone; D009638:Norepinephrine