Počet záznamů: 1  

Dual effects of muscarinic M2 acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists

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    SYSNO ASEP0142132
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JOstatní články
    NázevDual effects of muscarinic M2 acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists
    Tvůrce(i) Michal, Pavel (FGU-C) RID
    Lysíková, Michaela (FGU-C)
    Tuček, Stanislav (FGU-C)
    Zdroj.dok.British Journal of Pharmacology - ISSN 0007-1188
    Roč. 132, č. 6 (2001), s. 1217-1228
    Poč.str.12 s.
    Jazyk dok.eng - angličtina
    Země vyd.GB - Velká Británie
    Klíč. slovacyclic AMP ; muscarinic receptors ; CHO cells
    Vědní obor RIVED - Fyziologie
    CEPGA309/99/0214 GA ČR - Grantová agentura ČR
    IAA7011910 GA AV ČR - Akademie věd
    CEZAV0Z5011922 - FGU-C
    AnotaceMuscarinic M2 receptors normally inhibit the production of cyclic AMP via Gi proteins, but a stimulatory component occurs in their effect at high agonist concentrations, believed to be based on the activation of Gs proteins. We investigated the conditions which determine the occurrence and extent of the stimulatory component in CHO cells stably expressing muscarinic M2 receptors. Biphasic concentration-response curves (decline followed by return towards control values) were obtained after 10 min incubation with carbachol, oxotremorine-M, acetylcholine, arecoline and arecaidine propargyl ester, but the upward phase was missing with oxotremorine, methylfurmethide, furmethide and pentylthio-TZTP. Shortening the incubation favoured the occurrence of the stimulatory component. Carbachol (1 mM) and oxotremorine-M (1 mM) brought about net stimulation (above 100 of control) of cyclic AMP synthesis during 2 min incubations. The stimulatory components disappeared after the density of receptors had been lowered with oxyphenonium mustard. All agonists stimulated the synthesis of cyclic AMP in cells pretreated with pertussis toxin. Most differences between agonists regarding the stimulatory component of their effect on cyclic AMP synthesis could be explained by differences in their efficacy and the induced receptor internalisation. We propose that the Gs-mediated stimulatory component of the effect of muscarnic M2 receptors on cyclic AMP synthesis only occurs if the density of activated receptors is high enough to saturate the Gi proteins and proportionate to the receptors´ low affinity for the Gs proteins. It tends to be abolished by receptor internalisation.
    PracovištěFyziologický ústav
    KontaktLucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
    Rok sběru2002