AGONIST AND ANTAGONIST PROPERTIES OF BETA(3)-ADRENOCEPTORS IN HUMAN OMENTAL AND MOUSE 3T3-L1 ADIPOCYTES

The pharmacological properties of the native human beta(3)-adrenocepto r are poorly defined, In the present study, the agonist and antagonist properties of beta(3)-adrenoceptors in human omental and mouse 3T3-L1 adipocytes were compared by measuring lipolysis in the absence or pre sence of adrenoceptor blockers. Methodological experiments revealed th at all three beta-adrenoceptors were functionally expressed in both ty pes of adipocytes. This makes the human and the mouse cells directly c omparable in pharmacological studies. CGP 12177 was a selective partia l beta(3)-adrenoceptor agonist in both cell types with a pD(2) of abou t 7.5. The order of potency of classical non-selective adrenoceptor ag onists, when determined during blockade of beta(1)-, beta(2)- and alph a(2)-adrenoceptors, was isoprenaline>noradrenaline>adrenaline in both human and 3T3-L1 adipocytes. This is different from the order of poten cy of the same agonists at the beta(1)- or beta(2)-adrenoceptors. The sensitivity of the beta(3)-adrenoceptor to these catecholamines, expre ssed as pD(2) values, were virtually identical in both adipocyte types . Isoprenaline, noradrenaline, and adrenaline were almost full agonist s in both cell types (intrinsic activity from 74% or 95%) during combi ned beta(1), beta(2)- and alpha(2)-adrenoceptor blockade. Antagonist p otencies (expressed as pA(2) and using CGP 12177 as agonist) at the be ta(3)-adrenoceptor were similar in both adipocyte types: bupranolol>pr opranolol>metoprolol. The corresponding pA(2) values for bupranolol, p ropanolol and metoprolol were about 7, 6 and 5, respectively in both s pecies. In conclusion, the pharmacological properties of classical cat echolamines, beta-adrenoceptor blockers and CGP 12177 are almost ident ical at the beta(3)-adrenoceptors of human omental adipocytes and 3T3- L1 adipocytes.