Abstract
3H-Yohimbine, a potent and selective pharmacological antagonist of α2-adrenergic receptors, labeled human platelet membrane α2-receptors with high affinity. Binding was rapid and reversible at 25°C. Both saturation and kinetic experiments indicated a single order of binding sites, with an equilibrium KD value of 1.0-1.5 nM. Low Mg2+ concentrations increased the KD for 3H-yohimbine without altering the Bmax. The 3H-yohimbine site exhibited α2-receptor specificity: (-)-norepinephrine and (-)-isoproterenol were 4.8 and 330 times less potent than (-)-epinephrine; (-)-catecholamines were 17-35 times more potent than corresponding (+)-catecholamines; the selective α1-antagonist prazosin was 340 times less potent than yohimbine. Catecholamine agonists exhibited shallow curves in inhibiting 3H-yohimbine binding, with pseudo-Hill coefficients (nH) of less than 1.0, whereas the nH of antagonists was 1.0. No specific binding of 3H-prazosin to platelet membranes was observed, indicating the absence of α1-receptors. 3H-Yohimbine labeled fewer platelet sites than did 3H-dihydroergocryptine under identical conditions (80 vs 130 receptors/ cell), and may be a more specific and useful antagonist probe of platelet α2-receptors than 3H-dihydroergocryptine.
Original language | English (US) |
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Pages (from-to) | 2705-2717 |
Number of pages | 13 |
Journal | Life Sciences |
Volume | 28 |
Issue number | 24 |
DOIs | |
State | Published - Jun 15 1981 |
Funding
This research was supported by USPHS grants NS-15591, MH-30059 and MH-30938, and a grant-in-aid from the American Heart Association. H.Y.M is recipient of USPHS RCSA MH-47808. We thank Joan Mitrius for excellent technical assistance.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- Pharmacology, Toxicology and Pharmaceutics(all)