Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F01%3A20010245" target="_blank" >RIV/67985823:_____/01:20010245 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors.

Original language description

To clarify the involvement of specific domains of muscarinic receptors in the action of allosteric modulators, muscarinic M3 receptors (on which allosteric interactions are weak) were genetically modified to become more similar to M2 receptors (on whichallosteric interactions are strong) and expressed in COS-7 cells. Affinity for allosteric modulator gallamine was 25-50x enhanced by modifications of the third external loop (o3) and the negative effect of gallamine on the affinity for classical antagonist N-[3H]methylscopolamine ([3H]NMS) was augmented. Affinity for alcuronium became 3 fold higher after the o3 loop of M3 receptors was made identical with the o3 loop of M2 receptors, and alcuronium acquired positive influence on the affinity for [3H]NMS. This is the first instance of inducing positive cooperativity on muscarinic receptors by genetic manipulation. Transferring whole o2 loop from M2 to M3 receptors substantially enhanced affinities for gallamine and alcuronium without aug

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

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Project

<a href="/en/project/GA309%2F99%2F0214" target="_blank" >GA309/99/0214: Allosteric regulation of muscarinic acetylcholine receptors</a><br>

Continuities

Z - Vyzkumny zamer (s odkazem do CEZ)

Publication year

2001

Confidentiality

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

Name of the periodical

Molecular Pharmacology

ISSN

0026-895X

e-ISSN

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Volume of the periodical

60

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

7

Pages from-to

761-767

UT code for WoS article

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EID of the result in the Scopus database

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