Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F02%3A20020014" target="_blank" >RIV/67985823:_____/02:20020014 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor.

Popis výsledku v původním jazyce

Xanomeline is a potent agonist that is functionally selective for muscarinic M(1) receptors. We have shown previously that a significant fraction of xanomeline binding to membranes of Chinese hamster ovary (CHO) cells expressing the M(1) receptors occursin a wash-resistant manner and speculated that this persistent binding likely does not take place at the primary binding site on the receptor. In the present work we investigated in depth the pharmacological characteristics of this unique mode of xanomeline binding and the effects of this binding on the interaction of classical competitive ligands with the receptor in CHO cells that express the M(1) muscarinic receptor. Onset of persistent binding of xanomeline to the M(1) muscarinic receptor was fastand was only slightly hindered by atropine. Its dissociation was extremely slow, with a half-life of over 30 h. Although persistently bound xanomeline strongly inhibited binding of the classical antagonist N-methylscopolamine (NMS) to the

Název v anglickém jazyce

Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor.

Popis výsledku anglicky

Xanomeline is a potent agonist that is functionally selective for muscarinic M(1) receptors. We have shown previously that a significant fraction of xanomeline binding to membranes of Chinese hamster ovary (CHO) cells expressing the M(1) receptors occursin a wash-resistant manner and speculated that this persistent binding likely does not take place at the primary binding site on the receptor. In the present work we investigated in depth the pharmacological characteristics of this unique mode of xanomeline binding and the effects of this binding on the interaction of classical competitive ligands with the receptor in CHO cells that express the M(1) muscarinic receptor. Onset of persistent binding of xanomeline to the M(1) muscarinic receptor was fastand was only slightly hindered by atropine. Its dissociation was extremely slow, with a half-life of over 30 h. Although persistently bound xanomeline strongly inhibited binding of the classical antagonist N-methylscopolamine (NMS) to the

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

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Projekt

<a href="/cs/project/GP305%2F01%2FD119" target="_blank" >GP305/01/D119: Nestandardní interakce mezi muskarinovými receptory a jejich agonisty a antagonisty</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2002

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Pharmacology and Experimental Therapeutics

ISSN

0022-3565

e-ISSN

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Svazek periodika

301

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1033-1041

Kód UT WoS článku

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EID výsledku v databázi Scopus

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