Abstract
The specific binding site for thromboxane A2 (TXA2) was studied in cultured vascular smooth muscle cells (VSMC) of the rat aorta. [3H]SQ29,548, a potent and selective TXA2 receptor antagonist, displayed high-affinity and specificity, as well as saturable and displaceable binding to rat VSMC in culture. Scatchard analysis of equilibrium binding at 24 degrees C revealed a single class of binding sites with a Kd of 1.7 nM and a Bmax of 8.0 fmol/10(6) cells. A series of TXA2 receptor antagonists completely suppressed [3H]SQ29,548 binding to rat VSMC, and the rank order of their inhibitory potencies (Ki) correlated well with the potencies for suppression of the U46619-induced contraction of rat thoracic aorta. These results suggest that specific binding sites for [3H]SQ29,548 represent the TXA2 receptor in rat VSMC.
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Animals
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Aorta
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Bridged Bicyclo Compounds, Heterocyclic
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Cells, Cultured
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Fatty Acids, Unsaturated
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Hydrazines / metabolism
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Kinetics
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Male
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Prostaglandin Endoperoxides, Synthetic / pharmacology
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Rats
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Rats, Inbred Strains
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Receptors, Prostaglandin / drug effects
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Receptors, Prostaglandin / metabolism*
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Receptors, Thromboxane
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Thromboxane A2 / analogs & derivatives
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Thromboxane A2 / antagonists & inhibitors
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Thromboxane A2 / pharmacology
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Fatty Acids, Unsaturated
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Hydrazines
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Prostaglandin Endoperoxides, Synthetic
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Receptors, Prostaglandin
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Receptors, Thromboxane
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Thromboxane A2
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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ONO 11120
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SQ 29548
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ONO 3708