![[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}
|
|
|
|
|
||
J Ellis and M Seidenberg
Department of Psychiatry, University of Vermont College of Medicine, Burlington 05405.
Although gallamine and a number of other compounds have been reported to slow the rate of dissociation of labeled ligands, especially [3H]N- methylscopolamine (NMS), from muscarinic receptors of heart and brain, there has been some dispute as to whether the dissociation of [3H]quinuclidinyl benzilate (QNB) is subject to such allosteric regulation. The present studies were intended to determine whether past discrepancies might be due to differences between tissues. We have found that gallamine modulates the dissociation of [3H]QNB from muscarinic receptors of the heart in a biphasic manner. Low concentrations (micromolar) accelerate the rate of dissociation, whereas higher concentrations (millimolar) slow it; at about 0.1 mM, the two effects cancel each other. Similar results were obtained with muscarinic receptors from the brainstem, but gallamine had only marginal effects on the dissociation of [3H]QNB in the forebrain. On the other hand, verapamil exerts only monophasic effects (slowing) on the dissociation of both [3H]NMS and [3H]QNB from heart receptors and gallamine slows the dissociation of [3H]NMS to a similar extent in all three tissues. Thus, it appears that past discrepancies in the literature can be attributed to the tissues and concentrations of gallamine that were used. Furthermore, the biphasic effects of gallamine suggest that there are multiple allosteric regulatory sites associated with muscarinic receptors.
This article has been cited by other articles:
|
|
 |
|
  X.-P. Huang and J. Ellis Mutational Disruption of a Conserved Disulfide Bond in Muscarinic Acetylcholine Receptors Attenuates Positive Homotropic Cooperativity between Multiple Allosteric Sites and Has Subtype-Dependent Effects on the Affinities of Muscarinic Allosteric Ligands Mol. Pharmacol., March 1, 2007; 71(3): 759 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Lanzafame, P. M. Sexton, and A. Christopoulos Interaction Studies of Multiple Binding Sites on M4 Muscarinic Acetylcholine Receptors Mol. Pharmacol., August 1, 2006; 70(2): 736 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-P. Huang, S. Prilla, K. Mohr, and J. Ellis Critical Amino Acid Residues of the Common Allosteric Site on the M2 Muscarinic Acetylcholine Receptor: More Similarities than Differences between the Structurally Divergent Agents Gallamine and Bis(ammonio)alkane-Type Hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide Mol. Pharmacol., September 1, 2005; 68(3): 769 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jakubik, A. Krejci, and V. Dolezal Asparagine, Valine, and Threonine in the Third Extracellular Loop of Muscarinic Receptor Have Essential Roles in the Positive Cooperativity of Strychnine-Like Allosteric Modulators J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 688 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Christopoulos and T. Kenakin G Protein-Coupled Receptor Allosterism and Complexing Pharmacol. Rev., June 1, 2002; 54(2): 323 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Leppik, A. Mynett, S. Lazareno, and N. J. M. Birdsall Allosteric Interactions between the Antagonist Prazosin and Amiloride Analogs at the Human alpha 1A-Adrenergic Receptor Mol. Pharmacol., March 1, 2000; 57(3): 436 - 445. [Abstract] [Full Text]
|
|
|
|
|
|
A. Lanzafame, A. Christopoulos, and F. Mitchelson Three Allosteric Modulators Act at a Common Site, Distinct from that of Competitive Antagonists, at Muscarinic Acetylcholine M2 Receptors J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 278 - 285. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
