Aggregation of blood platelets by biogenic amines and its inhibition by antiadrenergic and antiserotoninergic agents

Barthel, Wolfgang; Markwardt, Fritz

doi:10.1016/0006-2952(74)90311-6

Cited by 42 publications

(13 citation statements)

References 31 publications

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“…The Kds reported here are in reasonable agreement with previously published binding data (7, 9) except for yohimbine which appears to be a more potent antagonist in the human platelet than in uterine (7) or vas deferens membranes (9). However, yohimbine has also been reported to be more potent than phentolamine in inhibiting platelet aggregation (2). (+) Propranolol is almost four orders of magnitude less potent than is phentolamine.…”

Section: Methodssupporting

confidence: 90%

“…4, reflects the known potency of these compounds in stimulating platelet aggregation and release (2,3). The binding data do not explain why a-adrenergic agonists such as phenylephrine and dopamine do not induce aggregation since they are similar to (-) norepinephrine in potency.…”

Section: Methodsmentioning

confidence: 98%

“…Thus, 8-adrenergic receptors have the potenicy series (-) isoproterenol > (-) epinepirine 2 (-) norepiinephirine, whereas a-adrenergic receptors respond to catecholamines with the order of potency (-) epinephrine > (-) norepinephrine > (-) isoproterenol (1). Indirect evidence suggests that catecholamiiine-iniduced aggregation of human platelets is mediated through an aadrenergic receptor: (a) (-) Epinephrine is most potent whereas (-) isoproterenol is virtually ineffective in inducing aggregation (2); (b) aggregation by epinephrine or norepinephrine is blocked by the a-adrenergic an-tagonists phentolamine or dihydroergotamine (2,3); (c) inhibition of adenylate cyclase activity in platelet lysates by epinephrine is blocked by a-adrenergic antagonists (4); (d) the ability of epinephrine to prevent the rise in platelet cyclic AMP induced by prostaglandin E1, an inhibitor of aggregation, is also blocked by a-adrenergic antagonists (5,6). Recent technical advances have made possible the direct study of a-adrenergic receptors using radioactive adrenergic antagonists which bind to the receptor site (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the Human Platelet α-Adrenergic Receptor

Alexander¹,

Cooper²,

Handin³

1978

J. Clin. Invest.

126

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A B S T R A C T Human platelets aggregate and undergo a release reaction wvhen inetubated wvith catecholamines. Indirect evidence indicates that these events are mediated through a-adrenergic receptors. We used [3H]dihydroergocryptine, an a-adrenergic antagonist, to identify binding sites on platelets that have the characteristics of a-adrenergic receptors. Catecholamines compete for the binding sites in a stereo-specific manner with the potency series of (-) epinephrine > (-) norepinephrine > (+) phenylephrine > (-) isoproterenol. The dissociation constant (Kd) of (-) ,M. Phentolamine and dihydroergocyrptine blocked this response, whereas (±) propranolol had no effect. (-) Epinephrine and (-) norepiniephrine inhibited basal and prostaglandin El-stimulated adenylate cyclase in a dose-related manner. The conicentrationi of( -) epiinephrinie inhibiting adenvlate cyclase 50% was 0.7 ,uM. This inhibitioni was also blocked by phentolamiiine and dihydroergocryptine btut not by (±) propranolol. The specificity of binding and the close correlationi with a-adrenergic receptor-mediated biochemical and physiological responses suggest that the [3H]dihydroergocryptine binding site represents, or is closely related to, the human platelet a-adrenergic receptor. The ability to assay this receptor directly and to correlate these data with independently measured se(uelae of receptor activation should facilitate increased understandinig of the physiology and pathophysiology of the hulmlani platelet a-adrenergic receptor.

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Section: Methodssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Characterization of the Human Platelet α-Adrenergic Receptor

Alexander¹,

Cooper²,

Handin³

1978

J. Clin. Invest.

126

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“…The most potent inhibitors of adrenaline-induced platelet aggregation are the dihydrogenated ergot alkaloids of the peptide type. Among the other ergoline derivatives tested, only lisuride has a stronger inhibitory effect than those o f natural ergot alkaloids.The biogenic amines, adrenaline and nor adrenaline, are known to induce aggregation of human blood platelets and to potentiate aggre gation induced by other stimuli (4,7,15,17,21,22). In thromboembolic diseases accom panied by an elevated catecholamine level in blood, adrenaline-mediated platelet reactions may enhance the risk of thrombosis.…”

mentioning

confidence: 99%

“…Therefore, tire pharmacological influence on adrenaline-induced changes in platelets pro vokes growing interest. Investigations on adren ergic agonists and antagonists have shown that adrenergic effects on platelets are mediated by stimulation of a-adrenoceptors and are in hibited by «-adrenergic antagonists which block the adrenergic receptor sites on the platelet membrane (4,17,21,22). «-Adrenoceptors of platelets have been characterized using the labelled ligands 3H-dihydroergokryptine and 3H-dihydroergonine (1,13,14,20).…”

mentioning

confidence: 99%

Studies on the Inhibition of Adrenaline-Induced Aggregation of Blood Platelets

Glusa¹,

Markwardt²,

Barthe³

1979

Pharmacology

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α-Adrenoceptors of platelets seem to differ from those of other cell types. The inhibitory effect of α-adrenoceptor-blocking agents on adrenaline-induced aggregation of human platelets does not parallel that on adrenaline-induced contraction of rabbit aortic strips. The most potent inhibitors of adrenaline-induced platelet aggregation are the dihydrogenated ergot alkaloids of the peptide type. Among the other ergoline derivatives tested, only lisuride has a stronger inhibitory effect than those of natural ergot alkaloids.

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Does dihydroergotamine potentiate the thromboprophylactic effect of dextran 70? A controlled prospective study in general and hip surgery

Bergqvist¹,

Lindblad²,

et al. 1984

Journal of British Surgery

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In a prospective randomized controlled study on postoperative thromboembolism, 259 patients undergoing elective general surgery, emergency general surgery, total hip replacement or hip fracture surgery were given thromboembolic prophylaxis with either a combination of dextran 70 and dihydroergotamine (DHE) or with dextran 70 alone. 500 ml dextran 70 was infused twice on the day of operation, once on postoperative days 1 and 3, and also on day 5 if the patient was still confined to bed. 0.5 mg DHE was given s.c. twice daily starting before operation and continued for 3 or 5 postoperative days. In hip fracture patients prophylaxis was started as soon as the diagnosis was made. 500 ml dextran 70 was given every other day before operation. DHE was given twice daily if so indicated from randomization. The patients were screened for deep-vein thrombosis (DVT) with the 125I-labelled fibrinogen test for 8 days and followed for one month postoperatively. In hip fracture surgery the incidence of DVT was significantly reduced by the combination of dextran 70 and DHE compared to dextran 70 alone (1/32 vs. 11/36, P = 0.003). However, this synergistic effect of DHE could not be detected in the other patient groups. Fatal pulmonary embolism did not occur. No severe side effects attributable to prophylaxis were noted in either group.

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Aggregation of blood platelets by biogenic amines and its inhibition by antiadrenergic and antiserotoninergic agents

Cited by 42 publications

References 31 publications

Characterization of the Human Platelet α-Adrenergic Receptor

Characterization of the Human Platelet α-Adrenergic Receptor

Studies on the Inhibition of Adrenaline-Induced Aggregation of Blood Platelets

Does dihydroergotamine potentiate the thromboprophylactic effect of dextran 70? A controlled prospective study in general and hip surgery

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