Agonistic and antagonistic effects of various ?-adrenergic agonists in human platelets

Lasch, Peter; Jakobs, Karl H.

doi:10.1007/bf00498981

Cited by 75 publications

(37 citation statements)

References 23 publications

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“…This departure cannot be attri- Figure 7 Schild plots for antagonism of the aggregatbuted to non-specific effects since both these latter ory response to adrenaline by UK-12767 ( proposed by Cusack & Hourani (1982a, b) although the approach we have adopted is very similar to that used by these latter workers. It is notable in this context that an earlier study by Lasch & Jakobs (1979) using a spectrum of a-adrenoceptor antagonists suggested a reasonable correlation between the IC50 values for their inhibition of the aggregatory and adenylate cyclase responses. Hence distinction between two receptors having a similar pharmacological profile may require screening of a large number of drugs as has been the case here.…”

Section: Resultsmentioning

confidence: 70%

“…Thus Glusa & Markwardt (1981) found that guanabenz, guanafacine and oxymetazoline are unable to cause platelet aggregation when added alone but are able to enhance the response to a sub-optimal concentration of ADP or thrombin. Jakobs (1978) and Lasch & Jakobs (1979) have also documented the inability of a number of o2-adrenoceptor agonists e.g. clonidine, oxymetazoline, to cause platelet aggregation when added in the absence of a second agonist such as ADP and also their failure to cause inhibition of adenylate cyclase .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of α₂‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Clare

Scrutton

Thompson

1984

British J Pharmacology

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Section: Resultsmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Effects of α₂‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Clare

Scrutton

Thompson

1984

British J Pharmacology

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“…Furthermore, only adrenaline was tested in the present study. Other clinically used adrenergic agents such as noradrenaline also need to be evaluated, although in vitro data suggest that noradrenaline is not as potent as adrenaline in inducing aggregation of untreated platelets 11, 15, 16…”

Section: Discussionmentioning

confidence: 99%

“…Supplementation with adrenaline, which is commonly used in cardiac surgery during and after cardiopulmonary bypass to maintain blood pressure, has previously been shown to potentiate platelet aggregation induced by ADP in healthy subjects11, 12 and in clopidogrel‐treated patients 13. In the present study, we hypothesized that adrenaline would potentiate ADP‐induced platelet aggregation and activation in patients with ongoing ASA and ticagrelor treatment, since the platelet membrane express adrenergic α 2A ‐receptors 11, 14, 15, 16. To test this hypothesis, we performed an in vitro study using blood samples from ACS patients on ongoing DAPT with ASA and ticagrelor.…”

Section: Introductionmentioning

confidence: 89%

Adrenaline enhances in vitro platelet activation and aggregation in blood samples from ticagrelor‐treated patients

Singh

Malm

Ramström

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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BackgroundTemporarily improved platelet reactivity may reduce the bleeding in patients on antiplatelet therapy who have ongoing bleeding or who are in need of acute surgery. Adrenaline can bind to adrenergic α2A‐receptors on platelets and potentially enhance platelet reactivity.ObjectiveTo assess if adrenaline can improve adenosine diphosphate (ADP)‐induced platelet aggregation and activation in blood samples from patients on dual antiplatelet therapy with acetylsalicylic acid (ASA) and the ADP‐receptor antagonist ticagrelor.MethodsBlood samples were collected from a total of forty acute coronary syndrome patients on dual antiplatelet therapy with ASA and ticagrelor. ADP‐induced platelet aggregation (by impedance aggregometry) and activation (by flow cytometry) were assessed before and after supplementation with adrenaline and/or platelet concentrate.ResultsAdrenaline supplementation (770 nmol L−1) increased median ADP‐induced aggregation from 15 (25‐75th percentiles: 10‐20) to 26 (18‐38) aggregation units. The effect was independent of concomitant platelet supplementation. Adrenaline also increased ADP‐induced platelet activation: from 40% (36‐54%) to 83% (74‐88%) platelets with active fibrinogen receptor (binding PAC‐1) and from 13% (7‐21%) to 35% (18‐50%) P‐selectin‐expressing platelets.ConclusionsAdrenaline potentiated ADP‐induced platelet aggregation and activation in blood samples from ticagrelor‐treated patients. Adrenaline infusion may be a new method to enhance platelet function in ticagrelor‐treated patients who are in need of acute surgery or have ongoing bleeding. In vivo studies are needed to confirm the present results.

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“…Some selective ax-agonists, e.g. clonidine and phenylephrine, mimic only part of the response to the natural agonist and hence act as partial agonists at the platelet a-adrenoceptors (Newman, Williams, Bishopric & Lefkowitz, 1978;Hsu, Knapp & Halushka, 1979) although a contrary view has been expressed (Jakobs, 1978;Lasch & Jakobs, 1979). The properties of the platelet a-adrenoceptors appear in many respects to correspond to the pre-synaptic and postsynaptic types as proposed by Langer (1974).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Selective Α‐adrenoceptor Agonists and Antagonists With Human and Rabbit Blood Platelets

Grant

Scrutton

1980

British J Pharmacology

109

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The selectivity of α‐adrenoceptors mediating the pro‐aggregatory response of human and rabbit platelets to adrenaline and the conditions required to permit expression of an aggregatory response to partial agonists at these α‐adrenoceptors have been studied. Yohimbine causes effective blockade of the pro‐aggregatory responses whereas indoramin and prazosin are ineffective. The clonidine analogue, UK‐14304, is nearly as effective as adrenaline in inducing an aggregatory response in human platelets and a pro‐aggregatory response in rabbit platelets. Cross‐tachyphylaxis between adrenaline and UK‐14304 has been demonstrated. Clonidine is a weak agonist for the pro‐aggregatory response of rabbit platelets and in some donors for the aggregatory response of human platelets. Methoxamine induces a pro‐aggregatory response in human platelets which is blocked by indoramin or prazosin but not by yohimbine. No such response to methoxamine is observed in rabbit platelets. The divalent cation ionophore, A‐23187, induces an aggregatory response to clonidine (in platelets from a non‐responsive donor), phenylephrine and methoxamine in human platelets and to adrenaline, UK‐14304 and clonidine in rabbit platelets. A secretory response to clonidine is also induced by A‐23187 in human platelets. The adenylate cyclase inhibitor, SQ‐22536, is ineffective in either inducing a response to the α‐agonists or potentiating the effect of A‐23187. The aggregatory responses to adrenaline and UK‐14304 in rabbit platelets and to clonidine in human and rabbit platelets, which can be induced by A‐23187, are blocked by yohimbine but not by prazosin or indoramin. From these studies we conclude that the pro‐aggregatory responses of human and rabbit platelets to adrenaline are mediated primarily by α2‐adrenoceptors. The presence of α1‐adrenoceptors on human platelets is confirmed but these receptors do not appear to be present on rabbit platelets. The conditions required for expression of an aggregatory response to partial agonists at the human and rabbit platelet α‐adrenoceptors implicate an increase in cytosolic Ca2+ concentration as a key event in stimulus‐response coupling but do not indicate such a role for depression of cyclic adenosine‐3′,5′‐monophosphate concentration.

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Agonistic and antagonistic effects of various ?-adrenergic agonists in human platelets

Cited by 75 publications

References 23 publications

Effects of α₂‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Effects of α₂‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Adrenaline enhances in vitro platelet activation and aggregation in blood samples from ticagrelor‐treated patients

Interaction of Selective Α‐adrenoceptor Agonists and Antagonists With Human and Rabbit Blood Platelets

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Agonistic and antagonistic effects of various ?-adrenergic agonists in human platelets

Cited by 75 publications

References 23 publications

Effects of α2‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Effects of α2‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Adrenaline enhances in vitro platelet activation and aggregation in blood samples from ticagrelor‐treated patients

Interaction of Selective Α‐adrenoceptor Agonists and Antagonists With Human and Rabbit Blood Platelets

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Effects of α₂‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Effects of α₂‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets