dihydroergotoxine and Drug-Hypersensitivity

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.

Topics: Adult; Aged; Aging; Binding, Competitive; Blood Platelets; Dihydroergotoxine; Drug Hypersensitivity; Epinephrine; Female; Humans; Male; Middle Aged; Phentolamine; Phenylephrine; Platelet Aggregation; Radioligand Assay; Receptors, Adrenergic, alpha