Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors.

Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors. Research Abstract Details 

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Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors. Abstract Text:

Yoshifumi Kawanabe,Yasuo Okamoto,Nobuo Hashimoto,Tomoh Masaki,

Endothelin-1 (ET-1) activates two types of Ca2+- permeable non-selective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC) in Chinese hamster ovary cells expressing endothelin-A receptors (CHOETAR), which couple with Gq, Gs and G12. The purpose of this study was to identify the G proteins involved in the activation of these Ca channels, using mutated ETARs with coupling to either Gq or Gs/G12 (designated ETAR(Delta)385 and SerETAR, respectively) and a dominant negative mutant of G12 (G12G228A). ETAR(Delta)385 is truncated downstream of Cys385 in the C-terminal as palmitoylation sites, whereas SerET(A)R is unpalmitoylated because of substitution of all the cysteine residues to serine (CysCys --> SerSer). ET-1 activated SOCC in CHO-ET(A)R(Delta)385. In CHO-SerET(A)R or CHO-ET(A)R pretreated with U73122, an inhibitor of phospholipase C, ET-1 activated NSCC-1. ET-1 activated SOCC in CHO-ETAR microinjected with G12G228A. Moreover, ET-1 activated NSCC-1 in CHO-ETAR treated with LY 294002, the phosphoinositide 3-kinase inhibitor. These results indicate that NSCC-1 is activated via a G12-dependent pathway, NSCC-2 via Gq/phospholipase C-dependent and G12-dependent pathways, and SOCC via a Gq-phospholipase C-dependent pathway. In addition, NSCC-2 and SOCC are stimulated by ET-1 via a phosphoinositide 3-kinase-dependent cascade, whereas NSCC-1 is stimulated via a phosphoinositide 3-kinase-independent cascade.

Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors. Publishing Authors By Initials

Y Kawanabe,Y Okamoto,N Hashimoto,T Masaki,

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Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of cardiovascular pharmacology

VOLUME: 44 Suppl 1

Page Numbers: S219-23

Journal Abbreviation: J. Cardiovasc. Pharmacol.

ISSN: 1533-4023

DAY: 19

MONTH: Nov

YEAR: 2004

Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors. Information

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LANGUAGE: eng

NlmUniqueID: 7902492

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Grant and Affiliation Information for Molecular mechanisms for activation of voltage-independent Ca2+ channels by endothelin-1/endothelin-A receptors.

AFFILIATION: Department of Neurosurgery and Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan. kawanabe@takatsuki.jrc.or.jp

Country: United States

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MEDLINETA: J Cardiovasc Pharmacol

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