Age-associated increments in human platelet alpha-adrenoceptor capacity. Possible mechanism for platelet hyperactivity to epinephrine in aging man.
In order to evaluate the effects of aging on platelet alpha-adrenergic receptor function, we have examined the binding of [3H]dihydroergocryptine ( [3H]DHE), a nonselective alpha-adrenergic antagonist, to crude platelet membrane at 25 degrees C in 28 subjects of various ages (mean 48, range 21-77 years) and platelet aggregatory response to epinephrine in other 32 subjects of various ages (mean 51, range 27-82 years). The average values of the binding capacity and affinity for [3H]DHE showed 218 +/- 56 fmol/mg protein (mean +/- SD) and 1.80 +/- 0.20 nM, respectively. There was a significant correlation between the binding capacity for [3H]DHE and age (r = 0.654, p less than 0.001). On the contrary, no significant correlation was found between the binding affinity for [3H]DHE and age (r = 0.273, p greater than 0.1). Exaggerated aggregatory response to epinephrine with advancing age was also demonstrated in this study (r = 0.716, p less than 0.001). Thus, the demonstration of increased alpha-adrenergic receptor capacity in aging man offers a possible explanation for the observed age-associated hyperactivity of the platelets to epinephrine.
D000328:Adult; D000368:Aged; D000375:Aging; D001667:Binding, Competitive; D001792:Blood Platelets / Q000032:analysis* / Q000187:drug effects; D004088:Dihydroergotoxine / Q000494:pharmacology; D004342:Drug Hypersensitivity; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*
D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D010656:Phenylephrine; D004837:Epinephrine; D010646:Phentolamine