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 ASEP 0142132 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Ostatní články Název Dual 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. - : Wiley - ISSN 0007-1188
Roč. 132, č. 6 (2001), s. 1217-1228Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova cyclic AMP ; muscarinic receptors ; CHO cells Vědní obor RIV ED - Fyziologie CEP GA309/99/0214 GA ČR - Grantová agentura ČR IAA7011910 GA AV ČR - Akademie věd CEZ AV0Z5011922 - FGU-C Anotace Muscarinic 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2002
Počet záznamů: 1