Regulation of platelet function by catecholamines in the cerebral vasculature of the rabbit

Abstract

In-labelled platelets were monitored continuously in the cerebral and pulmonary vascular beds of anaesthetized rabbits. Dopamine can, depending upon the concentration, either potentiate or inhibit thrombin-induced platelet accumulation in the cerebral vasculature of rabbits by unknown mechanisms. The eects of speci®c adrenergic and dopaminergic receptor antagonists were tested upon dopamine's actions on intracarotid (i.c.) thrombin-induced (80 u kg 71 ) platelet accumulation in the cerebral vasculature. The eect of adrenaline on the response to thrombin in this vascular bed was also investigated. 2 Thrombin-induced platelet accumulation was signi®cantly (P50.01) potentiated by dopamine (100 mg kg 71 min 71 , i.c.) and this eect was signi®cantly inhibited by infusion of the a-adrenoceptor antagonist, phentolamine. 3 A higher dose of dopamine (2 mg kg 71 min 71, i.c.) inhibited thrombin-induced platelet accumulation. The b-adrenoceptor antagonist, propranolol, did not signi®cantly alter this inhibitory eect whereas it was abolished by the dopamine D1 selective antagonist, SCH23390. 4 Adrenaline (when administered i.c. by bolus injection or infusion) had no signi®cant eect on thrombin-induced accumulation at any of the doses tested. 5 Potentiation of in vivo platelet accumulation by dopamine therefore seems to occur via aadrenergic receptors. However, the inhibitory eect of dopamine appears to be exerted via the activation of dopamine D1 receptors and not via b-adrenergic receptors. Our ®ndings con®rm that dopamine, but not adrenaline, can modify platelet function in the cerebral vasculature and these observations may have implications for current and potential therapeutic uses of dopamine and selective dopaminergic compounds.

RETRACTED ARTICLE: Dopamine receptors in human platelets

“…In vivo investigations reported that dopamine and dopamine receptor agonists can modify platelet function (Emerson et al 1997(Emerson et al , 1999. However, since the first reports of the presence of dopamine receptors in platelets De Keyser et al 1988), subsequent studies did not provide conclusive results (Boullin et al 1978;De Keyser et al 1989;Anfossi et al 1992Anfossi et al , 1993Dean et al 1992).…”

“…In vivo studies performed in rabbit cerebral and pulmonary vasculature have shown that dopamine modifies platelet aggregation as a function of concentration (Emerson et al 1997(Emerson et al , 1999. However, so far no conclusive evidence was provided on the expression of dopamine receptors by platelets and no information is available concerning dopamine receptor subtypes expressed by platelets.…”

“…Platelets possess sites of neurotransmitter uptake, storage and release and express multiple neurotransmitter receptors (Dean et al 1992;Andrews et al 1999;Emerson et al 1999;Fowler et al 1999;Gurguis et al 1999;Velayudhan et al 1999;Weizman et al 1999). Functional, pharmacological and biochemical studies have suggested a role of dopamine on platelet function (Daimon et al 1990;Emerson et al 1997Emerson et al , 1999.…”

“…Functional, pharmacological and biochemical studies have suggested a role of dopamine on platelet function (Daimon et al 1990;Emerson et al 1997Emerson et al , 1999. Altered platelet dopamine uptake was reported in Parkinson's and Huntington's diseases and in schizophrenia.…”

Dopamine D1-Like Receptors Suppress the Proliferation of Macrophages Induced by Ox-LDL

“…Dopamine receptors are expressed in many organs and tissues, and stimulation of the dopamine D 1 -like receptors prevents atherosclerosis via the inhibition of proliferation, migration and oxidation of VSMCs [12][13][14][15]. Dopamine D 1 -like receptors are present in VSMCs, platelets, lymphocytes and natural killer cells [33,34]. Our current study shows that both D 1 and D 5 receptors are expressed in macrophages.…”