MEPYRAMINE INHIBITS PLATELET-ACTIVATING FACTOR-INDUCED RABBIT PLATELET-AGGREGATION - ROLE OF INTRACELLULAR HISTAMINE

AIM: To study the possible role of intracellular histamine (HA) in pla telet activating factor (PAF)-induced platelet activation. METHODS: Wa shed rabbit platelet suspension was used to test the inhibitory effect of mepyramine (Mep, an H-1 receptor antagonist) on PAF-induced platel et aggregation. The thromboxane B-2 (TXB(2)) generation was measured b y radioimmunoassay and the intracellular calcium ([Ca2+](i)) concentra tion was determined by the specific fluorescence indicator Fura-2. RES ULTS: Mep >100 mu mol . L(-1) generated a concentration-dependent inhi bition on PAF-induced aggregation, with an IC50 value of 162 (95% conf idence limits: 114 - 232 mu mol . L(-1)). Cimetidine, an H-2 receptor antagonist, even up to 400 mu mol . L(-1) had no effect on it. Exogeno us HA (10 mu mol . L(-1)) and H-1 receptor agonist. 2-thia-zolylethyla mine had no energetic effect. alpha-Fluoro-methylhistidine, an inhibit or of histidine decarboxylase, did not inhibit platelet responses. How ever, in platelets permeabilized with saponin (8-10 mg . L(-1)), exoge nous HA attenuated the inhibitory effect of Mep to about 50% at a conc entration of 50 mu mol . L(-1). Preincubation of platelets with Mep (1 00 or 200 mu mol . L(-1)) resulted in an inhibition on TXB(2) generati on [Ca2+](i) elevation induced at PAF. CONCLUSION: Platelets activated by PAF is associated with an intracellular HA synthesis and release v ia a common pathway of TXB(2) generation and the rise of [Ca2+](i).