scholarly journals Molecular Mechanisms of Action and In Vivo Validation of an M4 Muscarinic Acetylcholine Receptor Allosteric Modulator with Potential Antipsychotic Properties

2009 ◽  
Vol 35 (4) ◽  
pp. 855-869 ◽  
Author(s):  
Katie Leach ◽  
Richard E Loiacono ◽  
Christian C Felder ◽  
David L McKinzie ◽  
Adrian Mogg ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Molecular Mechanisms ◽  
Muscarinic Acetylcholine Receptor ◽  
Mechanisms Of Action ◽  
Allosteric Modulator ◽  
Muscarinic Acetylcholine ◽  
In Vivo Validation

scholarly journals Molecular Mechanisms of Action of M5 Muscarinic Acetylcholine Receptor Allosteric Modulators

2016 ◽  
Vol 90 (4) ◽  
pp. 427-436 ◽  
Author(s):  
Alice E. Berizzi ◽  
Patrick R. Gentry ◽  
Patricia Rueda ◽  
Sandra Den Hoedt ◽  
Patrick M. Sexton ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Molecular Mechanisms ◽  
Muscarinic Acetylcholine Receptor ◽  
Mechanisms Of Action ◽  
Allosteric Modulators ◽  
Muscarinic Acetylcholine

In Vivo Determination of Muscarinic Acetylcholine Receptor Availability in Schizophrenia

2003 ◽  
Vol 160 (1) ◽  
pp. 118-127 ◽  
Author(s):  
Thomas J. Raedler ◽  
Michael B. Knable ◽  
Douglas W. Jones ◽  
Richard A. Urbina ◽  
Julia G. Gorey ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Muscarinic Acetylcholine Receptor ◽  
Muscarinic Acetylcholine

Molecular mechanism of doxorubicin-induced anticholinergic effect in guinea-pig atria

2000 ◽  
Vol 78 (6) ◽  
pp. 483-489 ◽  
Author(s):  
Yukio Hara ◽  
Kyosuke Temma ◽  
Zin Sekiya ◽  
Akihito Chugun ◽  
Hiroshi Kondo
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Acetylcholine Receptor ◽  
Action Potential Duration ◽  
Molecular Mechanisms ◽  
Muscarinic Acetylcholine Receptor ◽  
Anticholinergic Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Muscarinic Acetylcholine

The molecular mechanisms of anticholinergic actions of doxorubicin were examined by electrophysiological methods in atria and myocytes isolated from guinea-pig heart. A direct anticholinergic action of doxorubicin was confirmed with antagonistic action on carbachol-induced negative inotropic effect in atria. Both carbachol and adenosine produced shortening of action potential duration in atria measured by a microelectrode method. Doxorubicin (10-100 µM) inhibited the carbachol-induced action potential shortening in a concentration-dependent manner. However, doxorubicin did not antagonize the shortening elicited by adenosine. The whole-cell voltage clamp technique was performed to induce the muscarinic acetylcholine-receptor-operated K+ current (IK.ACh) in atrial myocytes loaded with GTP or GTPgammaS, a nonhydrolysable analogue of GTP. Doxorubicin (1-100 µM) suppressed carbachol-induced IK.ACh in a concentration-dependent manner (IC50 = 5.6 µM). In contrast, doxorubicin (10 and 100 µM) suppressed neither adenosine-induced IK.ACh nor GTPgammaS-induced IK.ACh. These results indicate that doxorubicin produces a direct anticholinergic effect through the muscarinic receptors in atrial myocytes.Key words: action potential duration, anticholinergic action, atrial cell, doxorubicin, the muscarinic acetylcholine-receptor-operated K+ current.

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