[Evidence for an alpha 2-blocking property of nicergoline by using antilipolytic alpha-adrenoceptors from adipose...

alpha-Adrenergic receptor which inhibit lipolysis in human and hamster fat cells are known to be of the alpha 2-type. By measuring the lipolytic activity on isolated fat cells and by studying the [3H]-yohimbine binding on the fat cell membranes, we tried to determine the alpha-adrenergic potency of the alpha-adrenolytic drug nicergoline. 1. Clonidine inhibits, in a concentration-dependent manner, the theophylline-stimulated lipolysis. This antilipolytic effect is suppressed by various alpha 2-adrenolytic agents but not by alpha 1-adrenolytic agents. Nicergoline is found to partially and competitively inhibit the antilipolytic effect of clonidine. 2. Specific binding of [3H]-yohimbine on fat cell membranes was a rapid and saturable process and was of high affinity (KD = 3.1 +/- 0.3 nM, Bmax = 615 +/- 90 f.mol./mg protein). 3. At low concentration, nicergoline displaced the specific binding of [3H]-yohimbine (EC50 = 0.440 microM). Compared to other alpha-adrenolytic agents, the affinity decreased in the following order: yohimbine greater than or equal to phentolamine greater than piperoxane greater than nicergoline much greater than prazosin. 4. The results show that the alpha-adrenergic antagonists capacity to suppress the antilipolytic effect of clonidine on isolated adipocytes is directly correlated with the ability to inhibit [3H]-yohimbine binding on fat cell membranes. Moreover we conclude that, on this model, nicergoline exhibits alpha 2-adrenolytic properties.