Effect of CL316,243, a highly specific beta(3)-adrenoceptor agonist, on lipolysis of epididymal, mesenteric and subcutaneous adipocytes in rats.

To clarify whether a beta(3)-adrenoceptor agonist is more lipolytic in the visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by CL316,243, a highly specific beta(3)-adrenoceptor agonist (relative selectivities of 0, 1 and 10,000 for beta(1)-, beta(2)- and beta(3)-receptors, respectively) was investigated in adipose tissue from rats. White adipocytes were prepared from the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar rats (weighing about 150 g). Our findings showed that lipolysis of white adipocytes was stimulated both by the non-specific beta-adrenoceptor agonist, isoproterenol, and by the beta(3)-specific adrenoceptor agonist, CL316,243, but the lipolytic sensitivity to CL316,243 was about 10 times greater than that to isoproterenol in these three adipose tissues. Both isoproterenol and CL316,243 induced more noticeable lipolysis in the epididymal and mesenteric than in the subcutaneous adipose cells in terms of the pD2 value [-log mol l-1 for EC50 (the concentration of an agonist giving half of its own maximum stimulation)]. These findings show that CL316,243 is more lipolytic in the visceral adipose cells than in the subcutaneous adipose cells, although epididymal adipose cells showed a high lipolytic response close to those observed in visceral adipose cells. CL316,243 may therefore be especially useful for the treatment of visceral fat type obesity related to various diseases.