Opioid-receptor (OR) signaling cascades in rat cerebral cortex and model cell lines : the role of plasma membrane structure.

Další autoři:	Ujčíková, H. Brejchová, J. Vošahlíková, M. Kagan, D. Dlouhá, K. Sýkora, Jan Merta, L. Drastichová, Z. Novotný, J. Ostašov, P. Roubalová, L. Parenti, M. Hof, M. Svoboda, Petr, 1974-
Jazyk:	angličtina
Předmět:	morfin proteomika cholesterol morphine proteomics články journal articles GPCR μ- δ- and κ-opioid receptors rat brain cortex adenylyl cyclase I and II proteomic analysis monovalent cations agonist-induced internalization plasma membrane structure membrane domains fluorescent probes
Druh dokumentu:	Non-fiction
Abstrakt:	Abstract: b1_Large number of extracellular signals is received by plasma membrane receptors which, upon activation, transduce information into the target cell interior via trimeric G-proteins (GPCRs) and induce activation or inhibition of adenylyl cyclase enzyme activity (AC). Receptors for opioid drugs such as morphine ( μ-OR, δ-OR and κ-OR) belong to rhodopsin family of GPCRs. Our recent results indicated a specific up-regulation of AC I (8-fold) and AC II (2.5-fold) in plasma membranes (PM) isolated from rat brain cortex exposed to increasing doses of morphine (10-50 mg/kg) for 10 days. Increase of ACI and ACII represented the specific effect as the amount of ACIII-ACIX, prototypical PM marker Na, K-ATPase and trimeric G-protein α and β subunits was unchanged. The up-regulation of ACI and ACII faded away after 20 days since the last dose of morphine. Proteomic analysis of these PM indicated that the brain cortex of morphine-treated animals cannot be regarded as being adapted to this drug because significant up-regulation of proteins functionally related to oxidativ e stress and alteration of brain energy metabolism occurred. The number of δ-OR was increased 2-fold and their sensitivity to monovalent cations was altered. Characterization of δ-OR-G-protein coupling in model HEK293 cell line indicated high ability of lithium to support affinity of δ-OR response to agonist stimulation. Our studies of PM structure and function in context with desensitization of GPCRs action were extended by data indicating part icipation of cholesterol-enriched membrane domains in agonist-specific internalization of δ-OR. In HEK293 cells stably expressing δ-OR-G i 1 α fusion protein, depletion of PM cholesterol was associated with the decrease in affinity of G-protein response to agonist stimulation, whereas maximum response was unchanged.
Databáze:	Katalog Knihovny AV ČR
Externí odkaz:	Online Access