Abstract
A series of studies were performed to determine the relationship between physiologic levels of circulating plasma norepinephrine and epinephrine and human platelet alpha-2 binding site number and the affinity (KD) of these sites for antagonist radioligands. In one study, alpha-2-adrenergic binding site number and affinity were compared using both [3H]yohimbine and [3H]dihydroergocryptine as radioligands. There was good absolute and relative comparison for binding site number, but only a relative relationship for KD. In 46 normal subjects, there was no significant relationship between site number or KD and age, plasma epinephrine, or plasma norepinephrine concentration. Even after plasma epinephrine was raised nearly 20-fold by means of an intravenous infusion for 4 h in seven normal subjects, neither sites (608 +/- 68 vs. 567 +/- 120 sites/platelet) nor KD (2.01 +/- 0.94 vs. 2.14 +/- 1.15 nM) were significantly changed. Similarly, neither sites (445 +/- 55 vs. 421 +/- 53 sites/platelet) nor KD (1.44 +/- 0.29 vs. 2.10 +/- 0.75 nM) were significantly changed in six normal subjects when plasma norepinephrine levels increased during oral administration of prazosin for 1 wk. Thus, in a cross-sectional analysis and after a change in plasma catecholamine concentrations, there was no relationship in normal subjects between platelet alpha-2 binding site number or affinity of these sites for antagonist radioligands and the circulating catecholamine levels to which the platelets were exposed. In a group (n = 7) of patients who lack epinephrine-induced platelet aggregation due to abnormal thrombopoiesis, binding site number was decreased (304 +/- 36 vs. 572 +/- 29 sites/platelet, P less than 0.001) and KD tended to be greater (8.69 +/- 2.44 vs. 5.40 +/- 0.31 nM, P = NS) than in normal subjects (n = 46), despite having similar plasma catecholamine levels. There was no difference in binding site number (491 +/- 116 sites/platelet) and KD (5.61 +/- 0.84 nM) in patients (n = 5) with autonomic insufficiency and low levels of upright plasma norepinephrine when compared with the normal subjects. Two patients were examined before and after the removal of a pheochromocytoma. Their binding site number and KD were normal before the operation and essentially unchanged after the tumor removal and fall of plasma catecholamines. Thus, this study demonstrates that within the physiologic and pathophysiologic range of plasma catecholamines (in men), there is no relationship between the circulating catecholamine concentration and either platelet alpha-2 adrenergic binding site number or the affinity of these sites for antagonist radioligands.
Full text
PDF









Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alexander R. W., Cooper B., Handin R. I. Characterization of the human platelet alpha-adrenergic receptor. Correlation of [3H]dihydroergocryptine binding with aggregation and adenylate cyclase inhibition. J Clin Invest. 1978 May;61(5):1136–1144. doi: 10.1172/JCI109028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BORN G. V., CROSS M. J. THE AGGREGATION OF BLOOD PLATELETS. J Physiol. 1963 Aug;168:178–195. doi: 10.1113/jphysiol.1963.sp007185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bygdeman S., Johnsen O. Studies on the effect of adrenergic blocking drugs on catecholamine-induced platelet aggregation and uptake of noradrenaline and 5-hydroxytryptamine. Acta Physiol Scand. 1969 Jan-Feb;75(1):129–138. doi: 10.1111/j.1748-1716.1969.tb04364.x. [DOI] [PubMed] [Google Scholar]
- Chobanian A. V., Tifft C. P., Sackel H., Pitruzella A. Alpha and beta adrenergic receptor activity in circulating blood cells of patients with idiopathic orthostatic hypotension and pheochromocytoma. Clin Exp Hypertens A. 1982;4(4-5):793–806. doi: 10.3109/10641968209061613. [DOI] [PubMed] [Google Scholar]
- Chuang D. M., Costa E. Evidence for internalization of the recognition site of beta-adrenergic receptors during receptor subsensitivity induced by (-)-isoproterenol. Proc Natl Acad Sci U S A. 1979 Jun;76(6):3024–3028. doi: 10.1073/pnas.76.6.3024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colucci W. S., Williams G. H., Braunwald E. Increased plasma norepinephrine levels during prazosin therapy for severe congestive heart failure. Ann Intern Med. 1980 Sep;93(3):452–453. doi: 10.7326/0003-4819-93-3-452. [DOI] [PubMed] [Google Scholar]
- Cooper B., Handin R. I., Young L. H., Alexander R. W. Agonist regulation of the human platelet alpha-adrenergic receptor. Nature. 1978 Aug 17;274(5672):703–706. doi: 10.1038/274703a0. [DOI] [PubMed] [Google Scholar]
- Cryer P. E., Silverberg A. B., Santiago J. V., Shah S. D. Plasma catecholamines in diabetes. The syndromes of hypoadrenergic and hyperadrenergic postural hypotension. Am J Med. 1978 Mar;64(3):407–416. doi: 10.1016/0002-9343(78)90220-6. [DOI] [PubMed] [Google Scholar]
- Daiguji M., Meltzer H. Y., U'Prichard D. C. Human platelet alpha 2-adrenergic receptors: labeling with 3H-yohimbine, a selective antagonist ligand. Life Sci. 1981 Jun 15;28(24):2705–2717. doi: 10.1016/0024-3205(81)90171-5. [DOI] [PubMed] [Google Scholar]
- Davies B., Sudera D., Sagnella G., Marchesi-Saviotti E., Mathias C., Bannister R., Sever P. Increased numbers of alpha receptors in sympathetic denervation supersensitivity in man. J Clin Invest. 1982 Apr;69(4):779–784. doi: 10.1172/JCI110516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Evans M. I., Halter J. B., Porte D., Jr Comparison of double- and single-isotope enzymatic derivative methods for measuring catecholamines in human plasma. Clin Chem. 1978 Apr;24(4):567–570. [PubMed] [Google Scholar]
- Galant S. P., Duriseti L., Underwood S., Insel P. A. Decreased beta-adrenergic receptors on polymorphonuclear leukocytes after adrenergic therapy. N Engl J Med. 1978 Oct 26;299(17):933–936. doi: 10.1056/NEJM197810262991707. [DOI] [PubMed] [Google Scholar]
- García-Sevilla J. A., Hollingsworth P. J., Smnith C. B. Alpha 2-adrenoreceptors on human platelets: selective labelling by [3H]clonidine and [3H]yohimbine and competitive inhibition by antidepressant drugs. Eur J Pharmacol. 1981 Sep 24;74(4):329–341. doi: 10.1016/0014-2999(81)90052-2. [DOI] [PubMed] [Google Scholar]
- Grant J. A., Scrutton M. C. Novel alpha2-adrenoreceptors primarily responsible for inducing human platelet aggregation. Nature. 1979 Feb 22;277(5698):659–661. doi: 10.1038/277659a0. [DOI] [PubMed] [Google Scholar]
- Hobbs D. C., Twomey T. M., Palmer R. F. Pharmacokinetics of prazosin in man. J Clin Pharmacol. 1978 Aug-Sep;18(8-9):402–406. doi: 10.1002/j.1552-4604.1978.tb02456.x. [DOI] [PubMed] [Google Scholar]
- Hoffman B. B., De Lean A., Wood C. L., Schocken D. D., Lefkowitz R. J. Alpha-adrenergic receptor subtypes: quantitative assessment by ligand binding. Life Sci. 1979 May 7;24(19):1739–1745. doi: 10.1016/0024-3205(79)90061-4. [DOI] [PubMed] [Google Scholar]
- Hoffman B. B., Lefkowitz R. J. Alpha-adrenergic receptor subtypes. N Engl J Med. 1980 Jun 19;302(25):1390–1396. doi: 10.1056/NEJM198006193022504. [DOI] [PubMed] [Google Scholar]
- Hoffman B. B., Michel T., Brenneman T. B., Lefkowitz R. J. Interactions of agonists with platelet alpha 2-adrenergic receptors. Endocrinology. 1982 Mar;110(3):926–932. doi: 10.1210/endo-110-3-926. [DOI] [PubMed] [Google Scholar]
- Hoffman B. B., Mullikin-Kilpatrick D., Lefkowitz R. J. Heterogeneity of radioligand binding to alpha-adrenergic receptors. Analysis of guanine nucleotide regulation of agonist binding in relation to receptor subtypes. J Biol Chem. 1980 May 25;255(10):4645–4652. [PubMed] [Google Scholar]
- Huang E. M., Detwiler T. C. Characteristics of the synergistic actions of platelet agonists. Blood. 1981 Apr;57(4):685–691. [PubMed] [Google Scholar]
- Izzo J. L., Jr, Horwitz D., Keiser H. R. Physiologic mechanisms opposing the hemodynamic effects of prazosin. Clin Pharmacol Ther. 1981 Jan;29(1):7–11. doi: 10.1038/clpt.1981.2. [DOI] [PubMed] [Google Scholar]
- Jaillon P. Clinical pharmacokinetics of prazosin. Clin Pharmacokinet. 1980 Jul-Aug;5(4):365–376. doi: 10.2165/00003088-198005040-00004. [DOI] [PubMed] [Google Scholar]
- Jakobs K. H., Rauschek R. [3H] Dihydroergonine binding to alpha-adrenergic receptors in human platelets. Klin Wochenschr. 1978;56 (Suppl 1):139–145. doi: 10.1007/BF01477465. [DOI] [PubMed] [Google Scholar]
- Kafka M. S., Tallman J. F., Smith C. C., Costa J. L. Alpha-adrenergic receptors on human platelets. Life Sci. 1977 Nov 15;21(10):1429–1438. doi: 10.1016/0024-3205(77)90197-7. [DOI] [PubMed] [Google Scholar]
- Karliner J. S., Motulsky H. J., Insel P. A. Apparent "down-regulation" of human platelet alpha 2-adrenergic receptors is due to retained agonist. Mol Pharmacol. 1982 Jan;21(1):36–43. [PubMed] [Google Scholar]
- Kaywin P., McDonough M., Insel P. A., Shattil S. J. Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet alpha-adrenergic receptors. N Engl J Med. 1978 Sep 7;299(10):505–509. doi: 10.1056/NEJM197809072991002. [DOI] [PubMed] [Google Scholar]
- Lynch C. J., Steer M. L. Evidence for high and low affinity alpha 2-receptors. Comparison of [3H]norepinephrine and [3H]phentolamine binding to human platelet membranes. J Biol Chem. 1981 Apr 10;256(7):3298–3303. [PubMed] [Google Scholar]
- Mills D. C., Roberts G. C. Effects of adrenaline on human blood platelets. J Physiol. 1967 Nov;193(2):443–453. doi: 10.1113/jphysiol.1967.sp008369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Motulsky H. J., Insel P. A. [3H]Dihydroergocryptine binding to alpha-adrenergic receptors of human platelets. A reassessment using the selective radioligands [3H]prazosin, [3H]yohimbine, and [3H]rauwolscine. Biochem Pharmacol. 1982 Aug 15;31(16):2591–2597. doi: 10.1016/0006-2952(82)90705-5. [DOI] [PubMed] [Google Scholar]
- Motulsky H. J., Shattil S. J., Insel P. A. Characterization of alpha 2-adrenergic receptors on human platelets using [3H]yohimbine. Biochem Biophys Res Commun. 1980 Dec 31;97(4):1562–1570. doi: 10.1016/s0006-291x(80)80044-1. [DOI] [PubMed] [Google Scholar]
- Mukherjee A. Characterization of alpha 2-adrenergic receptors in human platelets by binding of a radioactive ligand [3H]yohimbine. Biochim Biophys Acta. 1981 Aug 17;676(2):148–154. doi: 10.1016/0304-4165(81)90182-3. [DOI] [PubMed] [Google Scholar]
- Newman K. D., Williams L. T., Bishopric N. H., Lefkowitz R. J. Identification of alpha-adrenergic receptors in human platelets by [3H]dihydroergocryptine binding. J Clin Invest. 1978 Feb;61(2):395–402. doi: 10.1172/JCI108950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'BRIEN J. R. SOME EFFECTS OF ADRENALINE AND ANTI-ADRENALINE COMPOUNDS ON PLATELETS IN VITRO AND IN VIVO. Nature. 1963 Nov 23;200:763–764. doi: 10.1038/200763a0. [DOI] [PubMed] [Google Scholar]
- Santi D. V., Sibley C. H., Perriard E. R., Tomkins G. M., Baxter J. D. A filter assay for steroid hormone receptors. Biochemistry. 1973 Jun 19;12(13):2412–2416. doi: 10.1021/bi00737a007. [DOI] [PubMed] [Google Scholar]
- Shattil S. J., McDonough M., Turnbull J., Insel P. A. Characterization of alpha-adrenergic receptors in human platelets using [3H]clonidine. Mol Pharmacol. 1981 Jan;19(1):179–183. [PubMed] [Google Scholar]
- Snavely M. D., Motulsky H. J., O'Connor D. T., Ziegler M. G., Insel P. A. Adrenergic receptors in human and experimental pheochromocytoma. Clin Exp Hypertens A. 1982;4(4-5):829–848. doi: 10.3109/10641968209061616. [DOI] [PubMed] [Google Scholar]
- Stein L., Henry D. P., Weinberger M. H. Increase in plasma norepinephrine during prazosin therapy for chronic congestive heart failure. Am J Med. 1981 Apr;70(4):825–832. doi: 10.1016/0002-9343(81)90539-8. [DOI] [PubMed] [Google Scholar]
- Strittmatter W. J., Davis J. N., Lefkowitz R. J. alpha-Adrenergic receptors in rat parotid cells. II. Desensitization of receptor binding sites and potassium release. J Biol Chem. 1977 Aug 10;252(15):5478–5482. [PubMed] [Google Scholar]
- Tohmeh J. F., Cryer P. E. Biphasic adrenergic modulation of beta-adrenergic receptors in man. Agonist-induced early increment and late decrement in beta-adrenergic receptor number. J Clin Invest. 1980 Apr;65(4):836–840. doi: 10.1172/JCI109735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsai B. S., Lefkowitz R. J. Agonist-specific effects of guanine nucleotides on alpha-adrenergic receptors in human platelets. Mol Pharmacol. 1979 Jul;16(1):61–68. [PubMed] [Google Scholar]
- Ziegler M. G., Lake C. R., Kopin I. J. The sympathetic-nervous-system defect in primary orthostatic hypotension. N Engl J Med. 1977 Feb 10;296(6):293–297. doi: 10.1056/NEJM197702102960601. [DOI] [PubMed] [Google Scholar]