Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F15%3A00448654" target="_blank" >RIV/67985823:_____/15:00448654 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.phrs.2015.04.002" target="_blank" >http://dx.doi.org/10.1016/j.phrs.2015.04.002</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.phrs.2015.04.002" target="_blank" >10.1016/j.phrs.2015.04.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms

Popis výsledku v původním jazyce

We mutated key amino acids of the human variant of the M-1 muscarinic receptor that target ligand binding, receptor activation, and receptor-G protein interaction. We compared the effects of these mutations on the action of two atypical M-1 functionallypreferring agonists (N-desmethylclozapine and xanomeline) and two classical non-selective orthosteric agonists (carbachol and oxotremorine). Mutations of D105 in the orthosteric binding site and mutation of D99 located out of the orthosteric binding sitedecreased affinity of all tested agonists that was translated as a decrease in potency in accumulation of inositol phosphates and intracellular calcium mobilization. Mutation of D105 decreased the potency of the atypical agonist xanomeline more than that of the classical agonists carbachol and oxotremorine. Mutation of the residues involved in receptor activation (D71) and coupling to G-proteins (R123) completely abolished the functional responses to both classical and atypical agonists

Název v anglickém jazyce

Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms

Popis výsledku anglicky

We mutated key amino acids of the human variant of the M-1 muscarinic receptor that target ligand binding, receptor activation, and receptor-G protein interaction. We compared the effects of these mutations on the action of two atypical M-1 functionallypreferring agonists (N-desmethylclozapine and xanomeline) and two classical non-selective orthosteric agonists (carbachol and oxotremorine). Mutations of D105 in the orthosteric binding site and mutation of D99 located out of the orthosteric binding sitedecreased affinity of all tested agonists that was translated as a decrease in potency in accumulation of inositol phosphates and intracellular calcium mobilization. Mutation of D105 decreased the potency of the atypical agonist xanomeline more than that of the classical agonists carbachol and oxotremorine. Mutation of the residues involved in receptor activation (D71) and coupling to G-proteins (R123) completely abolished the functional responses to both classical and atypical agonists

Druh

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

CEP obor

ED - Fyziologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Pharmacological Research

ISSN

1043-6618

e-ISSN

—

Svazek periodika

97

Číslo periodika v rámci svazku

Jul 2015

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

27-39

Kód UT WoS článku

000357347600004

EID výsledku v databázi Scopus

2-s2.0-84928612821