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

Kód výsledku v 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>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

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/GA309%2F99%2F0214" target="_blank" >GA309/99/0214: Alosterická regulace muskarinových receptorů</a><br>

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2001

Kód důvěrnosti údajů

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

Název periodika

Molecular Pharmacology

ISSN

0026-895X

e-ISSN

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Svazek periodika

60

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

761-767

Kód UT WoS článku

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EID výsledku v databázi Scopus

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