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Id: lil-428284
Autor: Thompson, M; White, T; Chini, E. N.
Título: Modulation of store-operated Ca2+ entry by cyclic-ADP-ribose
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;39(6):739-748, June 2006. graf.
Idioma: en.
Resumo: Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70 percent by several inhibitors of the RyR, including ryanodine (10 µM), dantrolene (10 µM), and ruthenium red (10 µM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8-Br-cADPR (100 µM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80 percent. Pre-incubation of cells with 100 µM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 µM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80 percent. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.
Descritores: Cálcio/metabolismo
ADP-Ribose Cíclica/metabolismo
Miócitos de Músculo Liso/metabolismo
Western Blotting
ADP-Ribose Cíclica/antagonistas & inibidores
ADP-Ribose Cíclica/farmacologia
Miócitos de Músculo Liso/efeitos dos fármacos
Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
Transdução de Sinais
Canais de Potencial de Receptor Transitório/metabolismo
Limites: Feminino
Responsável: BR1.1 - BIREME

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