Characterization of the slow calcium channel binding sites for ( sup 3 H)SR 33557 in rat heart sarcolemmal membranes

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Molecular Pharmacology; (USA)

OSTI ID:6150850

Chatelain, P; Beaufort, P; Meysmans, L; Clinet, M ^[1]

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1. Sanofi-Labaz Research Centre, Brussels (Belgium)

SR 33557 represents a new class of compounds (indolizine sulfone) that inhibit L-type Ca2+ channels. ({sup 3}H)SR 33557 has been shown to bind with high affinity (Kd congruent to 0.36 nM, calculated from saturation isotherms and association/dissociation kinetics) to a single class of sites in a purified preparation of rat cardiac sarcolemmal membranes. The binding was found to be saturable and reversible. The maximal binding capacity was in approximately 1:1 stoichiometry with that of other Ca2+ channel antagonists. Various divalent cations (Mg2+, Mn2+, Ca2+, Ba2+, and Cd2+) were shown to inhibit specific ({sup 3}H)SR 33557 binding, with Cd2+ being the most potent. Among several receptor or channel ligands (including omega-conotoxin and Na+ and K+ channel modulators), only the L-type Ca2+ channel antagonists were found to displace ({sup 3}H)SR 33557. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylbutylpiperidines were found to inhibit ({sup 3}H)SR 33557 in a noncompetitive manner as demonstrated by displacement and saturation experiments in addition to dissociation kinetics. From these results, we suggest that SR 33557 binds with high affinity to a unique site on the L-type Ca2+ channel found in rat cardiac sarcolemmal membranes.

• OSTI ID: 6150850
• Journal Information: Molecular Pharmacology; (USA), Vol. 39:1; ISSN 0026-895X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CATIONS
BIOLOGICAL EFFECTS
GLYCOPROTEINS
RECEPTORS
CHEMICAL COMPOSITION
AFFINITY
BARIUM COMPOUNDS
BIOCHEMICAL REACTION KINETICS
CADMIUM COMPOUNDS
CALCIUM COMPOUNDS
CELL MEMBRANES
HEART
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MAGNESIUM COMPOUNDS
MANGANESE COMPOUNDS
RATS
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TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CHARGED PARTICLES
HYDROGEN COMPOUNDS
IONS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
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