![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 294, Issue 3, 923-932, September 2000
1-Adrenergic Receptor: Evidence for Interaction with
Distinct Conformations of 1-Adrenergic
Receptors1
Cellular and Clinical Neurobiology Program, Department of
Psychiatry and Behavioral Neurosciences, Wayne State University School
of Medicine, Detroit, Michigan
Pharmacological responses to aryloxypropanolamines were examined in
cells expressing rat or human 
1-adrenergic receptors (ARs) using adenylyl cyclase assays. The aryloxypropanolamines CGP
12177 and LY 362884, originally developed as 3-AR
agonists, were found to stimulate the 1-AR.
Interestingly, both CGP 12177 and LY 362884 exhibited an anomalous
biphasic effect on 1-AR. Low concentrations of either
CGP 12177 or LY 362884 potently blocked isoproterenol-induced
stimulation of 1-AR, whereas higher concentrations of
these compounds stimulated the 1-AR. The unusual
interaction of these aryloxypropanolamine ligands with the
1-AR was further characterized using -AR antagonists.
Activation of 1-AR by CGP 12177 or LY 362884 was
observed to be significantly more resistant to blockade by -AR
antagonists compared with activation by catecholamines. These results
suggest that catecholamines and aryloxypropanolamines interact with
distinct active conformations of the 1-AR: a state that
is responsive to catecholamines and is blocked with high affinity by
CGP 12177 and LY 362884, and a novel state that is activated by
aryloxypropanolamines but is resistant to blockade by standard -AR
antagonists. Moreover, dependence of antagonist affinity on agonist
structure is unprecedented, and its implications on the use of -AR
agonists such as CGP 12177 in receptor classification are discussed.
This article has been cited by other articles:
|
|
 |
|
  J. G. Baker, R. G. W. Proudman, N. C. Hawley, P. M. Fischer, and S. J. Hill Role of Key Transmembrane Residues in Agonist and Antagonist Actions at the Two Conformations of the Human {beta}1-Adrenoceptor Mol. Pharmacol., November 1, 2008; 74(5): 1246 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Baker and S. J. Hill A Comparison of the Antagonist Affinities for the Gi- and Gs-Coupled States of the Human Adenosine A1-Receptor J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 218 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Floreani, G. Froldi, L. Quintieri, K. Varani, P. A. Borea, M. T. Dorigo, and P. Dorigo In Vitro Evidence That Carteolol Is a Nonconventional Partial Agonist of Guinea Pig Cardiac {beta}1-Adrenoceptors: A Comparison with Xamoterol J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1386 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Baker Evidence for a Secondary State of the Human {beta}3-Adrenoceptor Mol. Pharmacol., December 1, 2005; 68(6): 1645 - 1655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Baker Site of Action of {beta}-Ligands at the Human {beta}1-Adrenoceptor J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1163 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Leblais, F. Pourageaud, M. D. Ivorra, C. Guibert, R. Marthan, and B. Muller Role of {alpha}-Adrenergic Receptors in the Effect of the {beta}-Adrenergic Receptor Ligands, CGP 12177, Bupranolol, and SR 59230A, on the Contraction of Rat Intrapulmonary Artery J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 137 - 145. [Abstract] [Full Text]
|
|
|
|
|
|
J. G. Baker, I. P. Hall, and S. J. Hill Agonist and Inverse Agonist Actions of {beta}-Blockers at the Human {beta}2-Adrenoceptor Provide Evidence for Agonist-Directed Signaling Mol. Pharmacol., December 1, 2003; 64(6): 1357 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Baker, I. P. Hall, and S. J. Hill Influence of Agonist Efficacy and Receptor Phosphorylation on Antagonist Affinity Measurements: Differences between Second Messenger and Reporter Gene Responses Mol. Pharmacol., September 1, 2003; 64(3): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Baker, I. P. Hall, and S. J. Hill Agonist Actions of "{beta}-Blockers" Provide Evidence for Two Agonist Activation Sites or Conformations of the Human {beta}1-Adrenoceptor Mol. Pharmacol., June 1, 2003; 63(6): 1312 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Jost, M. Fasshauer, C. R. Kahn, M. Benito, M. Meyer, V. Ott, B. B. Lowell, H. H. Klein, and J. Klein Atypical beta -adrenergic effects on insulin signaling and action in beta 3-adrenoceptor-deficient brown adipocytes Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E146 - E153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Guimaraes and D. Moura Vascular Adrenoceptors: An Update Pharmacol. Rev., June 1, 2001; 53(2): 319 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Granneman The putative {beta}4-adrenergic receptor is a novel state of the {beta}1-adrenergic receptor Am J Physiol Endocrinol Metab, February 1, 2001; 280(2): E199 - E202. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
