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-adrenoceptor 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 presence of adrenoceptor blockers. Methodological experiments revealed that all three beta-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 beta 3-adrenoceptor agonist in both cell types with a pD(2) of about 7.5. The order of potency of classical non-selective adrenoceptor agonists, when determined during blockade of beta 1-, beta 2- and alpha 2-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 beta 1- or beta 2-adrenoceptors. The sensitivity of the beta 3-adrenoceptor to these catecholamines, expressed as pD(2) values, 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 beta 1, beta 2- and alpha 2-adrenoceptor blockade. Antagonist potencies (expressed as pA(2) and using CGP 12177 as agonist) at the alpha 3-adrenoceptor were similar in both adipocyte types: bupranolol>propranolol>metoprolol. The corresponding pA(2) values for bupranolol, propanolol and metoprolol were about 7, 6 and 5, respectively in both species. In conclusion, the pharmacological properties of classical catecholamines, beta-adrenoceptor blockers and CGP 12177 are almost identical at the beta 3-adrenoceptors of human omental adipocytes and 3T3-L1 adipocytes.
Shimizu
M
M
Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
Blaak
E E
EE
Lonnqvist
F
F
Gafvels
M E
ME
Arner
P
P
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009852:Omentum / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D022702:Receptors, Adrenergic, beta-3; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D015016:Yohimbine; C026777:ICI 118551; D007545:Isoproterenol; C033394:CGP 12177