THE BINDING CHARACTERISTICS OF [3H]‐DIHYDROERGOCRYPTINE ON INTACT HUMAN PLATELETS

Abstract

1 We have characterized the binding of [³H]-dihydroergocryptine to intact human platelets. 2 The values of the association and dissociation rate constants, affinity and capacity of specific [³H]-dihydroergocryptine binding on intact cells closely resemble those previously reported on the human platelet lysate preparation. 3 The affinity of α-adrenoceptor antagonists, determined from inhibition of [³H]-dihydroergocryptine binding, is similar in intact and lysed platelet preparations, but the affinity of agonists is considerably lower in intact cells. 4 The potency of α-adrenoceptor antagonists as inhibitors of noradrenaline-induced platelet aggregation and as inhibitors of [³H]-dihydroergocryptine binding on intact platelets demonstrate a significant correlation (r = 0.92, P 3H]-dihydroergocryptine binding to platelets from a group of healthy, young, male subjects show a high degree of consistency both between subjects (K_d = 2.81 ± 0.27 nm; B_max = 63 ± 3 fmol/10⁸ platelet: mean ± s.e. mean, n = 10) and between sampling occasions in a single subject (K_d = 3.28nm ± 13%; B_max = 70 fmol/10⁸ platelet ± 16%: mean ± coefficient of variation, n = 5). 6 There is no significant difference in the binding capacity of platelets from a group of elderly male subjects (mean age 73) compared to those from young males (mean age 27) or elderly females (mean age 77). The affinity of binding is slightly but significantly (P < 0.05) higher in the elderly male group compared to the two other groups. 7 We conclude that [³H]-dihydroergocryptine binds to the α₂-adrenoceptor of intact human platelets which is responsible for noradrenaline-induced platelet aggregation. The high consistency of the binding characteristics of [³H]-dihydroergocryptine indicate that this assay may be useful as a monitor of platelet α-adrenoceptor sensitivity in clinical investigation.