Lack of desensitization of alpha-2-mediated inhibition of lipolysis in fat cells after acute and chronic treatment with clonidine.

The regulation of alpha-2 adrenoceptors and alpha-2 adrenergic responses by alpha-2 agonist treatment was investigated in in vitro and in vivo conditions. The alpha-2 adrenergic responsiveness of the adipocytes was tested with an alpha-2 agonist, clonidine, which inhibits, in a concentration-dependent manner, the lipolytic activity of the isolated fat cells incubated in the presence of adenosine deaminase (1-2 micrograms/ml). The effect of in vitro treatment of human s.c. fat cells and hamster adipocytes with clonidine as well as the incidence of chronic clonidine treatment (10 days) of golden hamsters were studied by testing lipolytic and antilipolytic responses of the isolated fat cells. Moreover, binding parameters were determined on the corresponding fat cell ghosts using [3H]clonidine and [3H]yohimbine. The preincubation of hamster (90 min) and human (3 hr) fat cells with clonidine did not modify the biological responses promoted by isoproterenol or clonidine. Binding analysis showed that the number of [3H]clonidine sites was reduced by 30 to 40% in human fat cell ghosts whereas [3H]yohimbine sites were unaffected by clonidine treatment. The chronic treatment of hamsters with clonidine (10 days, 200 micrograms/day) did not influence the lipolytic and antilipolytic responses of the fat cells. However, the number of alpha-2 adrenoceptor sites, identified by [3H]clonidine was reduced (40-50%). To conclude, short-term incubations of adipocytes with clonidine or long-term in vivo treatments with this drug are without any noticeable influence on the lipolytic and antilipolytic responses of human and hamster isolated fat cells. The reduction of [3H]clonidine binding sites described in both experiments must be questioned concerning its biological relevance.(ABSTRACT TRUNCATED AT 250 WORDS)