Is epinephrine-induced platelet aggregation autoregulated by its metabolic degradation products in vivo?

BACKGROUND

Catecholamines play an important role in platelet activation and aggregation, epinephrine being the most potent one. Catecholamines are substantially increased during stress, exercise or smoking and could result in clinically important platelet activation if their action was not rapidly regulated. In the present study the possible fast regulation of epinephrine-induced platelet aggregation by its metabolic degradation products is investigated.

MATERIALS AND METHODS

Human platelet rich plasma (hPRP) and washed rabbit platelets(wRP) were used for the study. The platelets irreversible aggregation induced by epinephrine and ADP were monitored by an aggregometer prior to and after the addition of the catecholamines degradation products metanephrine, 3-methoxy-4-hydroxy-phenyl-glycole-aldehyde (MHPGA),3-methoxy-4-hydroxy-phenyl-mandelic acid (VMA) 3,4-dihydroxy phenyl glycole (DHPG),3,4-Dihydroxy-phenyl-glycole-aldehyde (DHPGA) and the trimethoxy-phenyl-methyl-piperazine(TMP), a known free radical scavenger and calcium antagonist. Linoleic acid-lipoxygenase reaction, in vitro was monitored in the presence and absence of VMA.

RESULTS

Metabolic degradation products possessing a methoxy group at position 3 of the phenolic ring markedly inhibited epinephrine and ADP-induced platelet aggregation at microM concentrations. The most potent inhibitor of both agonists was metahephrine, followed by MHPGA and VMA. TMZ also inhibited platelet aggregation at concentrations similar to VMA. Dihydroxy-phenyl compounds failed to induce any inhibition. None of the substances tested induced any aggregatory effect even at high concentrations (1 mM). VMA significantly inhibited linoleic acid-lipoxygenase reaction at 0.1 microM.

CONCLUSIONS

Results indicate that catecholamines' degradation products possessing methoxy (-OCH3) groups can rapidly inhibit in vitro and ex vivo epinephrine-induced platelet aggregation. The inhibitory effects of methoxy phenolic derivatives on epinephrine-induced platelet aggregation may possibly be attributed to their free radical scavenging properties. There is substantial evidence to conclude that an internal rapid autoregulation of epinephrine-induced platelet aggregation, caused by its metabolic degradation products, takes place in vivo.