The effects of the putative potassium channel activator WAY-120,491 on 86Rb efflux from the rabbit aorta

Journal Article · Fri Feb 01 00:00:00 EST 1991 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6011286

Lodge, N J; Cohen, R B; Havens, C N; Colatsky, T J ^[1]

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1. Wyeth-Ayerst Research, Princeton, NJ (USA)

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.

• OSTI ID: 6011286
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 256:2; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIHYPERTENSIVE AGENTS
BIOCHEMICAL REACTION KINETICS
POTASSIUM COMPOUNDS
MEMBRANE TRANSPORT
AORTA
DOSE-RESPONSE RELATIONSHIPS
RABBITS
RUBIDIUM 86
TRACER TECHNIQUES
VASODILATORS
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMALS
ARTERIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANS
RADIOISOTOPES
REACTION KINETICS
RUBIDIUM ISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques