Time-dependent inhibition of platelet aggregation by dopamine and 3-methoxytyramine. Important roles of their metabolites.
The effects of dopamine (DA) and 3-methoxytyramine (3MT) on arachidonic acid (AA)-, collagen-, and adenosine 5'-diphosphate (ADP)-induced rabbit platelet aggregation were studied in relation to their metabolites in vitro. DA and 3MT did not inhibit AA- and collagen-induced platelet aggregation immediately after addition of a low concentration, but inhibition did occur, in a time-dependent and concentration-dependent manner, when DA and 3MT were incubated in platelet-rich plasma (PRP). The concentration of DA and 3MT decreased time-dependently, and the main metabolites of DA and 3MT were 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3-methoxy-4-hydroxyphenylacetaldehyde (MOPAL), respectively, as determined by high performance liquid chromatography. These aldehydes were found to have potent inhibitory activities nearly equal to those of 3,4-dihydroxyphenylethanol (DOPET) and 3-methoxy-4-hydroxyphenylethanol (MOPET) on both AA- and collagen-induced platelet aggregation. DOPET and MOPET were detected only in small concentrations. Taking into account both the anti-platelet potency and the concentrations detected in PRP of DOPAL and MOPAL, it is concluded that the time-dependent inhibition of the platelet aggregation by DA and 3MT may be due to the mediation of their corresponding main metabolites, DOPAL and MOPAL, respectively, while the concentration-dependent inhibition by DA and 3MT seems to be largely due to an innate activity.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D013997:Time Factors
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; C001746:3-methoxytyramine; D004298:Dopamine