THE EFFECTS OF CETIEDIL AND ITS CONGENERS ON LEVCROMAKALIM-STIMULATEDRB-86 EFFLUX FROM SMOOTH AND SKELETAL-MUSCLE

The effects of cetiedil on leveromakalim-stimulated Rb-86 efflux from rat aorta, rat anococcygeus and frog sartorius muscle have been invest igated. In experiments on rat aorta, cetiedil inhibited the tracer eff lux stimulated by 10 mu M levcromakalim with an IC50 of 1.3 +/- 0.4 mu M. In the rat anococcygeus and frog sartorius 10 mu M cetiedil caused 67 +/- 11% and 84 +/- 4% inhibition of the responses to 10 mu M and 5 0 mu M levcromakalim respectively. The effect of two analogues of ceti edil, UCL 1285 (cetiedil methiodide) and UCL 1495 (triphenyl acetic ac id-2-N[5-ethyl-2-methylpiperidinoethyl] ester) were also tested on rat aorta. UCL 1285 caused inhibition of the response to 10 mu M levcroma kalim with an IC50 of approximately 6 mu M. In contrast, UCL 1495 (10 mu M) had no significant effect. It is concluded that cetiedil is an e ffective blocker of the action of levcromakalim in smooth and skeletal muscle but does not distinguish between tissues. The relative activit ies of cetiedil, UCL 1285 and UCL 1495 are discussed in relation to th eir activity at other cetiedil-sensitive K+ channels.