INVOLVEMENT OF ALPHA(2)-ADRENOCEPTORS AND G-PROTEINS IN THE MODULATION OF PLATELET SECRETION IN RESPONSE TO STREPTOCOCCUS-SANGUIS

In the presence of plasma, human platelets secrete the contents of the ir dense granules and then aggregate in response to certain strains of Streptococcus sanguis. After 2 to 5 min of incubation with streptococ ci, platelets from fast-responding donors will begin to aggregate. Slo w responders aggregate after a longer delay. Platelets may secrete aft er a short (fast responder) or long (stow responder) delay because of differences in the basal levels or responses to potentiating catechola mines. To test this hypothesis in vitro, endogenous basal catecholamin e levels in platelets and plasma from fast and slow responders were an alyzed by HPLC with electrochemical detection. The total basal concent ration of epinephrine in platelets plus plasma was fourfold higher in fast responders, with the platelet compartment showing the greatest di fference. The basal affinity of alpha2-adrenoreceptors in platelets fr om both groups was similar when estimated using a specific antagonist, [H-3]-yohimbine. Platelets from all donors showed decreased alpha2-ad renoreceptor affinity in the presence of low (2 nM), but not higher (1 0 nM), concentrations of added epinephrine. Platelets in the two group s were then compared for secretion of ATP. More ATP was secreted after a shorter delay from fast responding platelets, which was mimicked in slow responders by adding physiologically attainable levels (40 nM) o f epinephrine. Addition of the alpha2-antagonist, phentolamine (10 muM ) to the platelets of slow and fast responders completely inhibited or reduced secretion by one third, respectively. Therefore, alpha2-adren oreceptors modulate the secretory response of platelets to cells of S. sanguis. Modulation of secretion may involve coupling of the alpha2-a drenoreceptor and S. sanguis receptor via G proteins because secretion in response to S. sanguis was inhibitable by pertussis or cholera tox ins, or GTPgammaS.