Acute reduction in human platelet alpha 2-adrenoreceptor affinity for agonist by endogenous and exogenous...

The binding characteristics of l-epinephrine to intact human platelets were assessed under conditions of physiological and pharmacological variations in plasma catecholamine concentration. In competition with the alpha 2-adrenoreceptor antagonist yohimbine, mean platelet receptor affinity for l-epinephrine was decreased 3.4-fold after 2 h of upright posture and exercise. This change in agonist affinity correlated significantly with the increases in plasma epinephrine and norepinephrine that were stimulated by upright posture and exercise. Supine subjects infused with l-norepinephrine or l-epinephrine for 2 h also averaged a 3.3- and 2.7-fold decrease in platelet alpha 2-adrenoreceptor affinity for agonist with no change in receptor number or antagonist affinity. The alpha 2-adrenoreceptor agonist affinity changes were specific for alpha-agonists since they were blocked by phentolamine, and incubation with 10(-5) M isoproterenol produced no change in alpha 2-adrenoreceptor affinity for l-epinephrine. In vitro exposure of intact human platelets to 10(-6) to 10(-10) M l-epinephrine for 2 h produced a concentration-related decrease in alpha 2-adrenoreceptor affinity for agonist. In all three paradigms, average slope factors approached 1.0 as affinity decreased, which is consistent with a heterogeneous receptor population that becomes more homogeneous after agonist exposure. Incubation of platelet-rich plasma with 10(-6) to 10(-8) M l-epinephrine resulted in a dose- and time-related loss of aggregatory response to l-epinephrine; this demonstrates that agonist affinity changes are correlated with changes in receptor sensitivity. These observations demonstrate that physiological variations in plasma catecholamines acutely modulate the intact human platelet alpha 2-adrenoreceptor's affinity for agonist, and can thereby alter the sensitivity of platelets to alpha 2-adrenergic agonist.