THE EFFECT OF BRADYKININ AND SUBSTANCE-P ON THE ARACHIDONATE CASCADE OF PLATELETS

Several peptide receptors are expressed on the surface of platelets, i ncluding B-1 and NK1, through which Bk and SP might influence platelet functions including their arachidonate cascade. The metabolites of th e arachidonate cascade might play a regulatory role in the inter- and intracellular functions of platelets. Platelets were separated from fr esh rat blood by differential centrifugation. Platelets (10(8) ml(-1) in each sample) were preincubated with Bk or SP. The arachidonate casc ade was investigated with [1-C-14]arachidonic acid, as tracer substrat e. The synthesised [C-14]eicosanoids were isolated and quantitatively determined. Bradykinin elicited a biphasic dose-response curve in the formation of the vasoconstrictor and platelet aggregating thromboxane A(2) (TxA(2)). Bk both inhibited (10(-8) mol/l), and elevated (10(-6) mol/l) the synthesis of TxA(2) in the thrombocytes. The 12-HETE synthe sis 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-HE TE in platelets was stimulated by SP (10(-11), 10(-9) 10(-8) mol/l). T he synthesis of TxA(2) in platelets was either attenuated (10-12 mol/l ), or stimulated (10(-9) mol/l) by SP. According to our observations B k and SP might play a regulatory role in the activation or deactivatio n of platelets.