RT Journal Article
SR Electronic
T1 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
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1084
OP 1095
VO 285
IS 3
A1 Matthew V. Sennitt
A1 Alberto J. Kaumann
A1 Peter Molenaar
A1 Lee J. Beeley
A1 Paul W. Young
A1 John Kelly
A1 Helen Chapman
A1 Sian M. Henson
A1 John M. Berge
A1 David K. Dean
A1 Nikesh R. Kotecha
A1 Helen K. A. Morgan
A1 Harshad K. Rami
A1 Robert W. Ward
A1 Mervyn Thompson
A1 Shelagh Wilson
A1 Stephen A. Smith
A1 Michael A. Cawthorne
A1 Michael J. Stock
A1 Jonathan R. S. Arch
YR 1998
UL http://jpet.aspetjournals.org/content/285/3/1084.abstract
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