Effects of dopamine and selective dopamine agonists upon platelet accumulation in the cerebral and pulmonary vasculature of the rabbit

Abstract

1 A selection of novel compounds were shown to exhibit dopaminergic activity in vitro. 2 111 Indium-labelled platelets were continuously monitored in the cerebral and pulmonary vasculature of anaesthetized rabbits. The e ects of dopamine and selective dopamine receptor agonists on ADP and thrombin induced platelet accumulation were recorded. 3 Pretreatment with dopamine (2 mg kg 71 min 71 , i.v.) signi®cantly reduced ADP (20 mg kg 71 , i.v.) induced platelet accumulation in the pulmonary vasculature whereas lower doses had no e ect. 4 Dopamine (100 mg kg 71 min 71 intra-carotid, i.c.) potentiated thrombin (90 u kg 71 , i.c.) induced platelet accumulation in the cerebral vasculature whereas higher doses (1 ± 2 mg kg 71 min 71 ) inhibited accumulation. 5 The selective dopamine receptor agonists tested did not signi®cantly inhibit platelet accumulation induced by ADP or thrombin. Two of these selective agonists, at doses higher than the intended therapeutic doses, induced thrombocytopaenia and an associated increase in platelet accumulation in the lung in response to thrombin. 6 These results extend previous in vitro studies regarding the dual actions of dopamine upon platelets and show for the ®rst time the e ects of selective dopamine receptor agonists upon platelet aggregation in vivo.

RETRACTED ARTICLE: Dopamine receptors in human platelets

“…As mentioned above, although the existence of platelet dopamine and L-DOPA uptake system was extensively demonstrated (Boullin and O'Brien 1970;Copolov 1989a, 1989b;Dean et al 1992;Emerson et al 1997Emerson et al , 1999Martignoni et al 1999), data on the expression of dopamine receptors by platelets are conflicting (Boullin et al 1978;Khanna et al 1987;De Keyser et al 1988, 1989. Studies on the characterisation of platelet dopamine receptors were based on the use of radioligand binding assay techniques with the dopamine D1-like and D2-like receptor antagonists [ 3 H]SCH 23390 (De Keyser et al 1988, 1989 and [ 3 H]haloperidol or [ 3 H]spiperone (Boullin et al 1978;Khanna et al 1987) as radioligands.…”

“…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).…”

“…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.…”

“…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.…”

Interaction of Biogenic Amine Hormones with Acetaldehyde

“…In lieu of dopamine's integral part in positive reinforcement, these data suggest that alcohol intake is reinforced by the feel-good sensations as a result of DA's stimulated/increased release [20]. According to Emerson et al [21], pretreatment with dopamine alone in concentrations of 2 mg/kg/min (higher than therapeutic levels) increased platelet accumulation in the lungs in response to thrombin and induced thrombocytopenia. Blood levels of dopamine are also increased in patients with renal insufficiency [22].…”