The effect of bradykinin and substance P on the arachidonate cascade of platelets.
Several peptide receptors are expressed on the surface of platelets, including B1 and NK1, through which Bk and SP might influence platelet functions including their arachidonate cascade. The metabolites of the arachidonate cascade might play a regulatory role in the inter- and intracellular functions of platelets. Platelets were separated from fresh rat blood by differential centrifugation. Platelets (10(8) ml-1 in each sample) were preincubated with Bk or SP. The arachidonate cascade was investigated with [1-14C]arachidonic acid, as tracer substrate. The synthesised [14C]eicosanoids were isolated and quantitatively determined. Bradykinin elicited a biphasic dose-response curve in the formation of the vasoconstrictor and platelet aggregating thromboxane A2 (TxA2). Bk both inhibited (10(-8) mol/l), and elevated (10(-6) mol/l) the synthesis of TxA2 in the thrombocytes. The 12-HETE synthesis was inhibited by Bk (10(-8), 10(-7), 10(-5) mol/l); 12-HETE is an endogenous regulator of prostacyclin synthesis. The formation of 12-HETE in platelets was stimulated by SP (10(-11), 10(-9), 10(-8) mol/l). The synthesis of TxA2 in platelets was either attenuated (10(-12) mol/l), or stimulated (10(-9) mol/l) by SP. According to our observations Bk and SP might play a regulatory role in the activation or deactivation of platelets.
Gecse
A
A
Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Kis
B
B
Mezei
Z
Z
Telegdy
G
G
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology* / Q000502:physiology; D013928:Thromboxane A2 / Q000097:blood
D015777:Eicosanoids; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D018040:Receptors, Neurokinin-1; D016718:Arachidonic Acid; D013373:Substance P; D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001920:Bradykinin