Characterization of G proteins involved in activation of nonselective cation channels and arachidonic acid release by norepinephrine/alpha1A-adrenergic receptors |
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Authors: | Kawanabe Yoshifumi Hashimoto Nobuo Masaki Tomoh |
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Institution: | Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. ykawanabe@rics.bwh.harvard.edu |
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Abstract: | We demonstrated recently that norepinephrine activates Ca2+-permeable nonselective cation channels (NSCCs) in Chinese hamster ovary cells stably expressing 1A-adrenergic receptors (CHO- 1A). Moreover, extracellular Ca2+ through NSCCs plays essential roles in norepinephrine-induced arachidonic acid release. The purpose of the present study was to identify the G proteins involved in the activation of NSCCs and arachidonic acid release by norepinephrine. For these purposes, we used U73122, an inhibitor of phospholipase C (PLC), and dominant negative mutants of G12 and G13 (G12G228A and G13G225A, respectively). U73122 failed to inhibit NSCCs activation by norepinephrine. The magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO- 1A microinjected with G13G225A were smaller than those in CHO- 1A. In contrast, the magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO- 1A microinjected with G12G228A were similar to those in CHO- 1A. In addition, neither a Rho-associated kinase (ROCK) inhibitor nor a phosphoinositide 3-kinase inhibitor affected norepinephrine-induced extracellular Ca2+ influx. G13G225A, but not G12G228A, also inhibited arachidonic acid release partially. These results demonstrate that 1) the Gq/PLC-pathway is not involved in NSCCs activation by norepinephrine, 2) G13 couples with CHO- 1A and plays important roles for norepinephrine-induced NSCCs activation, 3) neither ROCK- nor PI3K-dependent cascade is involved in NSCCs activation, and 4) G13 is involved in norepinephrine-induced arachidonic acid release in CHO- 1A. norepinephrine; 1A-adrenergic receptor; nonselective cation channel; G13 protein; arachidonic acid release |
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