EFFECT OF CROMAKALIM AND PINACIDIL ON RB-86 EFFLUX FROM GUINEA-PIG URINARY-BLADDER SMOOTH-MUSCLE

Rb-86 efflux assay was used to investigate the effect of cromakalim, p inacidil and P1075 in guinea pig urinary bladder strips. The type of K channel opened by cromakalim and pinacidil was determined using speci fic K channel blockers through Rb-86 efflux assay in detrusor strips. Cromakalim, pinacidil and P1075 all three potassium channel openers (P COs) evoked a concentration-dependent increase in Rb-86 efflux in blad der strips. This increase in isotope release was inhibited by pretreat ment of bladder with 10 and 30 mu M glibenclamide suggesting that both cromakalim and pinacidil interact with ATP-sensitive K channels (K-AT P) Further, an increase in basal Rb-86 efflux was observed when 2-deox y-D-glucose was substituted for glucose together with 0.24 mu g/ml of oligomycin (known to lower intracellular ATP) indicating the presence of K-ATP channels in bladder smooth muscle. Charybdotoxin and apamin, blockers of large and small conductance Ca2+-dependent K channels, wer e found not to be involved in the action of these PCOs in bladder stri ps. alpha-Dendrotoxin, known to block voltage-dependent K channels, sl ightly reduced pinacidil-induced Rb-86 release without affecting croma kalim-induced Rb-86 efflux. Rb-86 efflux assay The present studies sho w that ATP-sensitive K channels are present in guinea pig urinary blad der and that cromakalim and pinacidil act by opening channel blockers these ATP-sensitive K channels in detrusor strips.