Inhibition of rabbit platelet aggregation by nucleoside 5'-alkylphosphates: correlation with inhibition of agonist-induced calcium influx.
We investigated the effects of uridine 5'-alkylphosphates on agonist-induced aggregation, increased intracellular calcium concentration [Ca(2+)](i), and Ca(2+) (Mn(2+)) influx in washed rabbit platelets. Uridine 5'-hexadecylphosphate (UMPC16) and uridine 5'-eicosylphosphate (UMPC20) at a concentration of 1 x 10(-5) M inhibited platelet aggregation induced by platelet-activating factor (PAF), thrombin, arachidonic acid, and ADP. UMPC16 did not cause significant interference in the binding of [(3)H-acetyl]PAF to platelets. The inhibition of PAF-induced platelet aggregation by UMPC16 was dependent upon the addition time; UMPC16 was ineffective at 60 sec when the extracellular calcium uptake reached the maximum level in PAF-stimulated platelets. Furthermore, UMPC16 inhibited guanosine 5'-O-(3-thiotriphosphate)-induced platelet aggregation but did not affect ionophore A23187- and calcium-independent agonist phorbol 12-myristate 13-acetate-induced platelet aggregation. UMPC16 markedly inhibited the Ca(2+) (Mn(2+)) influx induced by PAF and ADP, and partly inhibited the [Ca(2+)](i) increase induced by the receptor-mediated stimulation. On the other hand, UMPC16 did not affect the [Ca(2+)](i) increase and Ca(2+) (Mn(2+)) influx induced by ionomycin. These experiments suggest that inhibition of calcium influx associated with receptor-mediated platelet activation may be involved in the action of UMPC16.
Sugatani
J
J
Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 422-8526, Shizuoka, Japan. sugatani@ys7.u-shizuoka-ken.ac.jp
Iwai
T
T
Watanabe
M
M
Machida
K
K
Tanaka
T
T
Maeda
T
T
Miwa
M
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004347:Drug Interactions; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013917:Thrombin / Q000378:metabolism; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology
D009711:Nucleotides; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C409383:uridine 5'-hexadecylphosphate; D015759:Ionomycin; D000244:Adenosine Diphosphate; D014542:Uridine Monophosphate; D013917:Thrombin; D002118:Calcium