[Evidence for an alpha 2-blocking property of nicergoline by using antilipolytic alpha-adrenoceptors from adipose tissue].
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.
D000273:Adipose Tissue / Q000166:cytology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003000:Clonidine / Q000494:pharmacology; D006224:Cricetinae; D004873:Ergolines / Q000494:pharmacology*; D006801:Humans; D008066:Lipolysis / Q000187:drug effects*; D009530:Nicergoline / Q000378:metabolism / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D013806:Theophylline / Q000037:antagonists & inhibitors; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D004873:Ergolines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D013806:Theophylline; D009530:Nicergoline; D003000:Clonidine
Mise en évidence d'une potentialité alpha 2-bloquante de la nicergoline par utilisation du récepteur alpha-adrénergique du tissu adipeux.