Vinburnine decelerates [3H]N-methylscopolamine binding to recombinant human muscarinic M1-M4 acetylcholine receptors.
The kinetics of [3H]N-methylscopolamine binding to membranes of Chinese hamster ovary (CHO) cells expressing muscarinic M(1)-M(4) acetylcholine receptors was studied. [3H]N-methylscopolamine dissociation was used for the "single-point" analysis of allosteric modulation by vinburnine (L-eburnamonine). [3H]N-methylscopolamine dissociation was decelerated by vinburnine with EC(50) values of 29.5, 4.1, 9.5 and 15.0 microM for muscarinic M(1)-M(4) receptors, respectively. Acetylcholine doubled the EC(50) of vinburnine for muscarinic M(3) receptors. These kinetic EC(50) values correlated with equilibrium binding constants, supporting the ternary allosteric model. Vinburnine also decelerated the association of [3H]N-methylscopolamine binding, resulting in opposite cooperativity for muscarinic M(1) and M(2) receptors.
Maksay
Gábor
G
Department of Molecular Pharmacology, Chemical Research Center, Hungarian Academy of Sciences, H-1525, Budapest, POB 17, Hungary. maksay@chemres.hu
Bíró
Tímea
T
Kiss
Béla
B
D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D019832:N-Methylscopolamine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D043588:Receptor, Muscarinic M4 / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism; D014748:Vinca Alkaloids / Q000494:pharmacology*
D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D014748:Vinca Alkaloids; D014316:Tritium; C016422:eburnamonine; D019832:N-Methylscopolamine