Alterations by glyburide of effects of BRL 34915 and P 1060 on contraction, 86Rb efflux and the maxi-K+ channel in rat portal vein

Journal Article · Tue May 01 00:00:00 EDT 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:7016225

Hu, S L; Kim, H S; Okolie, P; Weiss, G B ^[1]

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1. CIBA-GEIGY Corporation, Summit, NJ (USA)

Effects of the K+ channel blocking agent, glyburide, on the actions of two K+ channel openers, BRL 34915 (cromakalim) and P 1060 (Leo), a potent pinacidil derivative (N-(t-butyl)-N{double prime}-cyano-N{prime}-3-pyridyl-guanidine), were ascertained. Tension responses and {sup 86}Rb fluxes in rat portal vein strips and single channel electrophysiological recordings in enzymatically dissociated rat portal vein cells were obtained. Glyburide (0.3 microM) increased spontaneous contractile activity and caused concentration-dependent shifts in the relaxation responses to BRL 34915 and P 1060. Increases in {sup 86}Rb efflux were obtained only at much higher concentrations of BRL 34915 or P 1060, and these increases were blocked only at higher concentrations of glyburide (5.0 microM). BRL 34915 and P 1060 specifically increase the open-state probability of the Ca+(+)-activated K+ (maxi-K+) channel, and these actions are blocked by glyburide and also by charybdotoxin. Changes in single channel activity and contractile responsiveness occur at similar concentrations of agonists and antagonists. Thus, the membrane channel in rat portal vein affected by glyburide, BRL 34915 and P 1060 appears to be the Ca+(+)-activated maxi-K+ channel (that does not show ATP dependence under the conditions of these experiments). Concentrations of agonists and antagonists effective on maxi-K+ channel activity correspond to those affecting contractile responsiveness and are lower than those eliciting changes in {sup 86}Rb flux.

• OSTI ID: 7016225
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 253:2; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PORINS
BIOLOGICAL EFFECTS
POTASSIUM COMPOUNDS
MEMBRANE TRANSPORT
VASODILATORS
BIOCHEMICAL REACTION KINETICS
CELL MEMBRANES
ELECTROPHYSIOLOGY
IN VITRO
MUSCLES
RATS
RUBIDIUM 86
TRACER TECHNIQUES
VASOCONSTRICTION
VEINS
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DRUGS
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHYSIOLOGY
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
RUBIDIUM ISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques