WAY 120,491 activates ATP-sensitive potassium channels in rat tail artery.
WAY 120,491 lowers blood pressure in a number of animal models. Its mechanism of action appears to be the selective opening of K+ channels in vascular smooth muscle cells. The patch clamp technique was used to determine the specific K+ channel affected by WAY 120,491 in isolated tail artery cells of the rat. In the inside-out configuration, WAY 120,491 caused a dose dependent partial reversal of the ATP-induced inactivation of channel activity. Glyburide (10 microM) almost completely inhibited the effect of WAY 120,491. WAY 120,491 had no effect on Ca-activated K+ channels inactivated by the absence of Ca2+. In the whole cell configuration, 10 microM WAY 120,491 increased outward K+ current. 10 microM glyburide completely reversed the increase in current. WAY 120,491 appears to be a relatively specific activator of ATP-sensitive K+ channels in vascular smooth muscle.
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Department of Physiology, University of Michigan, Ann Arbor 48109.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001158:Arteries; D001578:Benzopyrans / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D013623:Tail / Q000098:blood supply
D000959:Antihypertensive Agents; D001578:Benzopyrans; D007211:Indoles; D015221:Potassium Channels; C067406:WAY 120491; D000255:Adenosine Triphosphate; D005905:Glyburide