Regulation of platelet function by catecholamines in the cerebral vasculature of the rabbit.
1. 111In-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 effects of specific adrenergic and dopaminergic receptor antagonists were tested upon dopamine's actions on intracarotid (i.c.) thrombin-induced (80 u kg-1) platelet accumulation in the cerebral vasculature. The effect of adrenaline on the response to thrombin in this vascular bed was also investigated. 2. Thrombin-induced platelet accumulation was significantly (P<0.01) potentiated by dopamine (100 microgkg-1 min-1, i.c.) and this effect was significantly inhibited by infusion of the alpha-adrenoceptor antagonist, phentolamine. 3 A higher dose of dopamine (2 mg kg-1 min-1, i.c.) inhibited thrombin-induced platelet accumulation. The beta-adrenoceptor antagonist, propranolol, did not significantly alter this inhibitory effect whereas it was abolished by the dopamine D1 selective antagonist, SCH23390. 4 Adrenaline (when administered i.c. by bolus injection or infusion) had no significant effect on thrombin-induced accumulation at any of the doses tested. 5 Potentiation of in vivo platelet accumulation by dopamine therefore seems to occur via alpha-adrenergic receptors. However, the inhibitory effect of dopamine appears to be exerted via the activation of dopamine D1 receptors and not via beta-adrenergic receptors. Our findings confirm 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.
Emerson
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Sackler Institute of Pulmonary Pharmacology, Division of Pharmacology & Therapeutics, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College London, Manresa Road, London SW3 6LX.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007205:Indium Radioisotopes; D008297:Male; D011817:Rabbits
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D018492:Dopamine Antagonists; D007202:Indicators and Reagents; D007205:Indium Radioisotopes; D004298:Dopamine; D004837:Epinephrine