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

Result code in 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>
Result on the web
<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>

Result language
angličtina
Original language name
Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms
Original language description
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
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
ED - Physiology
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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