Potassium efflux enhancement by cromakalim (BRL 34915) in rabbit mesenteric artery: an indirect effect independent of calcium?
Experiments have been performed in order to investigate the calcium and exposure time dependency of cromakalim (BRL 34915)-stimulated rubidium efflux in rabbit isolated mesenteric artery. Removal of calcium from the bathing medium prolonged the effects of cromakalim on rubidium efflux. Lanthanum was without effect on cromakalim-induced efflux whilst high concentrations of nifedipine were required to produce a significant inhibitory effect. Decreasing the exposure time to cromakalim, either in the presence or absence of calcium, led to a progressive loss of the response. However, significant increases in rubidium efflux rate were observed after very short exposures (15 sec) to the drug. In normal medium, exposure to cromakalim resulted in an inhibition of a second response when the drug was reapplied. Blockade by tetraethylammonium of the initial rubidium efflux response to cromakalim did not reverse the inhibition of the second response. These results suggest that the stimulation by cromakalim of rubidium efflux in rabbit isolated mesenteric artery is independent of calcium influx and requires only a short initial exposure to the drug in order to develop a response. The development and maintenance of the response after the removal of the drug suggest that cromakalim does not directly interact with the potassium channel through which rubidium efflux enhancement is observed.
Coldwell
M C
MC
Beecham Pharmaceutical Research Division, Medicinal Research Centre, Harlow, Essex, U.K.
Howlett
D R
DR
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002021:Buffers; D002118:Calcium / Q000494:pharmacology*; D019806:Cromakalim; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism
D001578:Benzopyrans; D002021:Buffers; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D007811:Lanthanum; D009543:Nifedipine; D012413:Rubidium; D002118:Calcium