This paper is only available as a PDF. To read, Please Download here.
The widespread use of beta-adrenoceptor antagonists againist hypertension, angina pectoris and migraine or as a preventive treatment after myocardial infarction has encouraged us to investigate the effects of these drugs on platelet function. The aim of this study was to examine whether beta-blocking drugs interfere with platelet beta- adrenoceptors and whether this dependency is related to their selectivity for beta-adrenoceptor subtypes. Beta-adrenoceptor stimulation of human platelets with isoprenaline increased cyclic AMP (cAMP), which is known to inhibit platelet aggregation. Furthermore, our studies showed that cAMP formation was stimulated by non-selective and beta2-selective agonists, but not by the predominant beta-agonist prenalterol. Isoprenaline- stimulated cAMP formation was blocked by the non- selective beta-adrenoceptor antagonists propranolol, timolol, and alprenolol, while the betal-selective antagonists atenolol and metoprolol had no influence on an isoprenaline-induced cAMP formation. Receptor binding studies using (3H-dyhydroalprenolol revealed an IC50 value for propranolol of 85 nM, while metoprolol only displaced the bound (33H)-dihydroalprenolol at far higher concentrations (IC50, 20 μM). We conclude that the human platelet beta-adrenoceptors are mainly of the beta2 - subtype and that beta-adrenoceptor antagonists, especially the non-selective antagonists interfere with platelet function assessed as platelet cAMP formation.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Thrombosis Research
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Differentiation of receptor systems activated by sympathomimetic amines.Nature. 1967; 214: 597-598
- Some effects of adrenaline and anti adrenaline compounds on platelets in vitro and in vivo.Nature. 1963; 200: 763-764
- The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3′, 5′-cyclic monophosphate in platelets.Biochem. J. 1971; 121: 185-196
- Control of platelet responsiveness by agents that influence cyclic AMP metabolism.Ann. N.Y. Acad. Sci. 1972; 201: 391-399
- Studies on the effect of adrenergic blocking drugs on catecholamine-induced platelet aggregation and uptake by noradrenaline and 5-hydroxytryptamine.Acta Physiol. Scand. 1969; 75: 128-129
- Stereospecific (3H)-alprenol binding sites, beta-adrenergic receptors and adenyl cyclase.Biochem. Biophys. Res. Commun. 1974; 60: 700-709
- The effect of alpha-adrenergic agents on human platelet aggregation.J. Pharmacol. Exp. Ther. 1978; 208: 366-370
- Agonistic and antagonistic effects of various alpha-adrenergic agonists in human platelets.Naunyn-Schmiedeberg's Archs.Pharmacol. 1979; 306: 119-125
- Beta-adrenergic receptors in human platelets.J. Atheroscler. Res. 1969; 9: 171-177
- Characterization of alpha- and beta-adrenergic receptors linked to human platelet adenylate cyclase.Naunyn-Schmiedeberg's Archs. Pharmacol. 1978; 302: 285-291
- Platelet beta-adrenoceptors.Br. J. Pharmac. 1983; 79: 681-691
- Platelet aggregation and beta-blockers.Lancet. 1982; i: 224-225
- Effect of long-term beta-blockade with alprenolol on platelet function and fibrinolytic activity in patients with coronary heart disease.Eur. J. Clin. Pharmacol. 1981; 20: 245-250
- Effect of lithium on prostaglandin El-stimulated adenylate cyclase activity of human platelets.Biochem. Pharmacol. 1974; 23: 845-855
- A simple and inexpensive protein binding assay for cyclic Af-iP in biological materials.Acta pilarmacol. et toxicol. 1977; 40: 356-368
- Protein measurements with the folin phenol reagent.Biol. Chem. 1951; 193: 265-275
- Comparison of pharmacological and binding assays for ten beta-adrenoceptor blocking agents and two beta-adrenoceptor agonists.Br. J. Pharmac. 1980; 68: 563-659
- Prenalterol, a non-selective beta-adrenoceptor ligand with absolute beta1-selective partial agonist activity.J. Pharm. Pharmacol. 1980; 32: 661
- In vitro assessment of the selectivities of various beta-adrenergic blocking agents.Life Sciences. 1980; 27: 2078-2092
- Adrenoceptor blocking agents, compounds related to metoprolol.J. Med. Chem. 1981; 24: 451-454
- Demonstration of human platelet beta-adrenegenic receptors using labelled cyanopindolol and 125I-labelled hydroxybenzylpindolol.Biochim. Biophys Acta. 1982; 686: 240-244
- Binding of (3H)-dihydroalprenolol and (3H)-acetobutolol to human blood platelets is not related to occupancy of beta-adrenoceptors.Thromb. Res. 1983; 239: 583-594
- Anti-platelet activity of beta-adrenergic antagonists.in: Inhibition of thromboxane synthesis and platelet aggregation in patients receiving long-term propranolol treatment. 5th edition. Lancet. ii. 1981: 1382-1384
Accepted: July 2, 1985
Received: December 27, 1984
© 1985 Published by Elsevier Inc.