PT  - JOURNAL ARTICLE
AU  - N J Lodge
AU  - R B Cohen
AU  - C N Havens
AU  - T J Colatsky
TI  - The effects of the putative potassium channel activator WAY-120,491 on 86Rb efflux from the rabbit aorta.
DP  - 1991 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 639--644
VI  - 256
IP  - 2
4099  - http://jpet.aspetjournals.org/content/256/2/639.short
4100  - http://jpet.aspetjournals.org/content/256/2/639.full
SO  - J Pharmacol Exp Ther1991 Feb 01; 256
AB  - WAY-120,491 [(-)-(3S-trans)-2-[3,4-dihydro-3-hydroxy-2,2-dimethyl-6-(trifluoromet hox y)- 2H-1-benzopyran-4-yl]-2,3-dihydro-1H-isoindol-1-one] is a novel antihypertensive agent. We have investigated the effects of this compound on contractile force and 86Rb efflux, using the rabbit aorta, in order to assess its K channel activator properties. K channel blockers and ionic conditions thought to modulate specific K channel types have been used to provide insight into the K channel(s) affected by this compound. WAY-120,491 evoked relaxation of precontracted rabbit aortic rings and increased the rate of 86Rb efflux from strips of rabbit aorta; both effects occurring in a concentration-dependent manner. The WAY-120,491 (1 microM)-induced 86Rb efflux was inhibited by tetraethylammonium (IC50 = 0.38 mM), indicating that the increased efflux was mediated by K channels. Glyburide completely blocked the WAY-120,491 (1 microM)-evoked 86Rb efflux with 50% block occurring at a concentration of 0.48 microM. Glyburide also antagonized the WAY-120,491-induced relaxation of aortic rings. Omission of Ca from the solution bathing the aorta did not inhibit the WAY-120,491 induced 86Rb efflux but rather caused an augmentation of the response. It is concluded that WAY-120,491 may be classified as a K channel opener. Furthermore, the K channel upon which WAY-120,491 acts exhibits some characteristics normally associated with the ATP regulated K channel although the involvement of other K channel types has not been ruled out.