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Human blood platelets display alpha2-adrenergic receptors, which promote platelet aggregation and inhibit the adenylate cyclase. We investigated the effects of the antihypertensive agent clonidine and its analogue para-aminoclonidine on this receptor in the intact human platelet to determine their pharmacological effects and their ability to bind to the receptor by radioligand displacement. Both agents potentiated platelet aggregation induced by a submaximal concentration of ADP. Epinephrine-induced aggregation, on the other hand, was antagonized by clonidine and para-aminoclonidine in a dose-dependent fashion. Both agents inhibited the accumulation of cyclic AMP in platelets exposed to prostaglandin E1 and a phosphodiesterase inhibitor, but to a lesser extent than the inhibition caused by epinephrine. Both antagonized this excess inhibitory action of epinephrine. Clonidine and para-aminoclonidine blocked the binding of [3H]yohimbine (a selective alpha2-adrenergic antagonist) to intact platelets with half-maximal effects at 0.3 and 0.7 μM, respectively. No evidence for the existence of a second class of binding sites with high affinity for clonidine was seen in intact platelets, either by this technique or by direct binding of [3H]clonidine. It is concluded that these two agents are partial agonists for the alpha2-adrenergic receptors on blood platelets and that this receptor exists predominantly in the low-affinity state in the intact cell.
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- Clonidine.in: Scriabine A Pharmacology of Antihypertensive Drugs. Raven Press, New York1980: 55-78
- Localization of the hypotensive effect of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155, Catapresan).Eur J Pharmacol. 1969; 6: 8
- Evidence of an alpha-sympathomimetic component in the effects of catapresan on vasomotor centres: antagonism by piperoxane.Eur J Pharmacol. 1971; 14: 98
- Cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155). I. Peripheral sympathetic system.Eur J Pharmacol. 1968; 2: 333
- Alpha-adrenergic receptor subtypes: quantitative assessment by ligand binding.Life Sci. 1979; 24: 1739
- Role of phosphatidylinositol turnover in alpha1, and of adenylate cyclase inhibition in alpha2 effects of catecholamines.Life Sci. 1980; 26: 1183
- Alpha-noradrenergic receptor binding in mammalian brain: differential labeling of agonist and antagonist states.Life Sci. 1976; 19: 69
- The characteristics of [3H]clonidine binding to an alpha-adrenoceptor in membranes from guinea-pig kidney.Br J Pharmacol. 1979; 65: 663
- Binding of [3H]clonidine to an alpha-adrenoceptor in membranes of guinea-pig ileum.Naunyn-Schmiedebergs Arch Pharmacol. 1979; 309: 207
- Identification of alpha2-adrenergic receptors in human fat cell membranes by [3H]clonidine binding.Eur J Pharmacol. 1980; 67: 481
- Effects of catecholamines on the formation of adenosine 3′:5′-cyclic monophosphate in human blood platelets.Biochem J. 1971; 125: 377
- Effects of adrenaline on human blood platelets.J Physiol (Lond). 1967; 193: 443
- Use of [methyl-3H]yohimbine as a radioligand for alpha2-adrenoreceptors on intact platelets. Comparison with dihydroergocryptine.Thromb Res. 1981; 24: 31
- Characterization of alpha2-adrenergic receptors on human platelets using [3H]yohimbine.Biochem Biophys Res Commun. 1980; 97: 1562
- [3H]Para-amino-clonidine: a novel ligand which binds with high affinity to alpha-adrenergic receptors.Life Sci. 1979; 25: 769
- Alpha2-adrenergic receptors in neuroblastoma X glioma hybrid cells. Characterization with agonist and antagonist radioligands and relationship to adenylate cyclase.Mol Pharmacol. 1982; 21: 17
- Characterization of alpha-adrenergic receptors in human platelets using [3H]clonidine.Mol Pharmacol. 1981; 19: 179
- The effect of ATP on platelets: evidence against the central role of released ADP in primary aggregation.Blood. 1975; 46: 309
- Affinity chromatography of human platelet alpha2-adrenergic receptors.in: Proc Natl Acad Sci USA. 79. 1982: 7223
- Reduction of adenylate cyclase activity in lysates of human platelets by the alpha-adrenergic component of epinephrine.J Cyclic Nucleotide Res. 1976; 2: 381
- Solubilization of human platelet alpha-adrenergic receptors: evidence that agonist occupancy of the receptor stabilizes receptor-effector interactions.in: Proc Natl Acad Sci USA. 78. 1981: 4026
- Parallel observation of the occupancy of the alpha2-adrenergic receptor in intact platelets and its ability to inhibit the adenylate cyclase.Mol Pharmacol. 1982; 22: 574
- 2-Methylthioadenosine [B32P]diphosphate. An agonist and radioligand for the receptor that inhibits the accumulation of cyclic AMP in intact platelets.J Clin Invest. 1983; 73: 420
- Bidirectional collision coupling in the regulation of the adenylate cyclase: the allozyme hypothesis for receptor function.Mol Pharmacol. 1982; 22: 580
- Pharmacokinetics and concentration-effect relationships of intravenous and oral clonidine.Clin Pharmacol Ther. 1977; 21: 593
Accepted: July 12, 1983
Received: February 15, 1983
© 1983 Published by Elsevier Inc.