![[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. 54, Issue 5, 899-906, November 1998
-[35S]thiotriphosphate Binding to Liposomes
with Varying Muscarinic Receptor/Go Protein Stoichiometry
ek
Institute of Physiology, Academy of Sciences of the Czech Republic,
14220 Prague, Czechia (J.J., S.T.), and
Department of
Neurochemistry, Faculty of Medicine, University of Tokyo, Tokyo 113, Japan (T.H.)
We investigated whether alcuronium, an allosteric modulator of
muscarinic acetylcholine receptors, can induce receptor-mediated activation of Go proteins in liposomal membranes
incorporating purified M2 receptors and Go
proteins and whether its action is affected by the
receptor/Go protein (R/Go) ratio. The binding of guanosine-
-[35S]thiotriphosphate
([35S]GTPS) served as the indicator of G protein
activation. It was stimulated by empty receptors at high receptor
densities, and the dose-response curve was shifted to the left by the
agonist carbachol and to the right by the antagonist atropine. At an
R/Go ratio of 300:100, the rate of
[35S]GTPS binding was the same in the presence or
absence of 0.1 mM carbachol. Alcuronium increased the
binding of [35S]GTPS at R/Go ratios of
<3:100 and diminished it at R/Go ratios of >10:100,
similar to previous observations on intact cells expressing muscarinic
receptors at different densities. The apparent biphasicity of
alcuronium action indicates that the allosteric modulator has at least
two effects on muscarinic receptor/G protein interaction but its
mechanistic basis is unclear. The "active state" of muscarinic receptors induced by alcuronium probably is different from that induced
by carbachol. Changes in the densities of receptors and Go
proteins had little effect on the kinetics of
[35S]GTPS binding and on receptor affinity for
carbachol, provided the R/Go ratio was kept constant. This
suggests that the receptors and G proteins are located in microdomains
in which their concentrations remain constant, despite variations in
the amounts of lipidic membranes in the system.
This article has been cited by other articles:
|
|
 |
|
  E. Machova, J. Jakubik, E. E. El-Fakahany, and V. Dolezal Wash-Resistantly Bound Xanomeline Inhibits Acetylcholine Release by Persistent Activation of Presynaptic M2 and M4 Muscarinic Receptors in Rat Brain J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 316 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Michal, E. E. El-Fakahany, and V. Dolezal Muscarinic M2 Receptors Directly Activate Gq/11 and Gs G-Proteins J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 607 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Langmead, V. A. H. Fry, I. T. Forbes, C. L. Branch, A. Christopoulos, M. D. Wood, and H. J. Herdon Probing the Molecular Mechanism of Interaction between 4-n-Butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the Muscarinic M1 Receptor: Direct Pharmacological Evidence That AC-42 Is an Allosteric Agonist Mol. Pharmacol., January 1, 2006; 69(1): 236 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. May, Y. Lin, P. M. Sexton, and A. Christopoulos Regulation of M2 Muscarinic Acetylcholine Receptor Expression and Signaling by Prolonged Exposure to Allosteric Modulators J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 382 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jakubik, S. Tucek, and E. E. El-Fakahany Role of Receptor Protein and Membrane Lipids in Xanomeline Wash-Resistant Binding to Muscarinic M1 Receptors J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 105 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cordeaux, S. A. Nickolls, L. A. Flood, S. G. Graber, and P. G. Strange Agonist Regulation of D2 Dopamine Receptor/G Protein Interaction. EVIDENCE FOR AGONIST SELECTION OF G PROTEIN SUBTYPE J. Biol. Chem., July 27, 2001; 276(31): 28667 - 28675. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
