Agonist and Antagonist Properties of β3‐Adrenoceptors in Human Omental and Mouse 3T3‐L1 Adipocytes

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Abstract
The pharmacological properties of the native human β3‐adrenoceptor are poorly defined. In the present study, the agonist and antagonist properties of β3‐adrenoceptors in human omental and mouse 3T3‐L1 adipocytes were compared by measuring lipolysis in the absence or presence of adrenoceptor blockers. Methodological experiments revealed that all three β‐adrenoceptors were functionally expressed in both types of adipocytes. This makes the human and the mouse cells directly comparable in pharmacological studies. CGP 12177 was a selective partial p3‐adrenoceptor agonist in both cell types with a pD2of about 7.5. The order of potency of classical non‐selective adrenoceptor agonists, when determined during blockade of β1, β2‐ and α2‐adrenoceptors, was isoprenaline>noradrenaline>adrenaline in both human and 3T3‐L1 adipocytes. This is different from the order of potency of the same agonists at the β1or β2‐adrenoceptors. The sensitivity of the β3‐adrenoceptor to these catecholamines, expressed as pD2values, were virtually identical in both adipocyte types. Isoprenaline, noradrenaline, and adrenaline were almost full agonists in both cell types (intrinsic activity from 74% or 95%) during combined β1, β2‐ and α2‐adrenoceptor blockade. Antagonist potencies (expressed as pA2and using CGP 12177 as agonist) at the β3‐adrenoceptor were similar in both adipocyte types: bupranolol>propranolol>meto‐prolol. The corresponding pA2values for bupranolol, propanolol and metoprolol were about 7, 6 and 5, respectively in both species. In conclusion, the pharmacological properties of classical catecholamines, P‐adrenoceptor blockers and CGP 12177 are almost identical at the β3‐adrenoceptors of human omental adipocytes and 3T3‐L1 adipocytes.