PT  - JOURNAL ARTICLE
AU  - Matthew V. Sennitt
AU  - Alberto J. Kaumann
AU  - Peter Molenaar
AU  - Lee J. Beeley
AU  - Paul W. Young
AU  - John Kelly
AU  - Helen Chapman
AU  - Sian M. Henson
AU  - John M. Berge
AU  - David K. Dean
AU  - Nikesh R. Kotecha
AU  - Helen K. A. Morgan
AU  - Harshad K. Rami
AU  - Robert W. Ward
AU  - Mervyn Thompson
AU  - Shelagh Wilson
AU  - Stephen A. Smith
AU  - Michael A. Cawthorne
AU  - Michael J. Stock
AU  - Jonathan R. S. Arch
TI  - The Contribution of Classical (β<sub>1/2</sub>-) and Atypical β-Adrenoceptors to the Stimulation of Human White Adipocyte Lipolysis and Right Atrial Appendage Contraction by Novel  β<sub>3</sub>-Adrenoceptor Agonists of Differing Selectivities
DP  - 1998 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1084--1095
VI  - 285
IP  - 3
4099  - http://jpet.aspetjournals.org/content/285/3/1084.short
4100  - http://jpet.aspetjournals.org/content/285/3/1084.full
SO  - J Pharmacol Exp Ther1998 Jun 01; 285
AB  - The role of β3- and other putative atypical β-adrenoceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine β3-adrenoceptor (β3AR) agonists with varying intrinsic activities and selectivities for human cloned βAR subtypes. The ability to demonstrate β1/2AR antagonist-insensitive (β3 or other atypical βAR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective β3AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited β1/2AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full β3AR agonist elicited full lipolytic and inotropic responses that were sensitive to β1/2AR antagonism, despite it having very low efficacies at cloned β1- and β2ARs. A component of the response to another phenylethanolamine selective β3AR agonist (SB-215691) was insensitive to β1/2AR antagonism in some experiments. Because novel aryloxypropanolamine had a β1/2AR antagonist-insensitive inotropic effect, these results establish more firmly that β3ARs mediate lipolysis in human white adipocytes, and suggest that putative ‘β4ARs‘ mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned βARs which βARs will mediate responses to agonists in tissues that have a high number of β1- and β2ARs or a low number of β3ARs. The American Society for Pharmacology and Experimental Therapeutics