Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 서석효 | * |
dc.contributor.author | 오세관 | * |
dc.contributor.author | 최신규 | * |
dc.contributor.author | 박성희 | * |
dc.date.accessioned | 2016-08-28T12:08:28Z | - |
dc.date.available | 2016-08-28T12:08:28Z | - |
dc.date.issued | 2012 | * |
dc.identifier.issn | 1043-6618 | * |
dc.identifier.other | OAK-8842 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/222700 | - |
dc.description.abstract | Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K Ca3.1 channels and vascular smooth muscle contraction. K Ca3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of K Ca3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit K Ca3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC 50) of modafinil for the current inhibition was 6.8 ± 0.7 nM. The protein kinase A (PKA) activator forskolin also inhibited K Ca3.1 currents. The inhibitory effects of modafinil and forskolin on K Ca3.1 currents were blocked by the PKA inhibitors PKI 14-22 or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated K Ca3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of K Ca3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits K Ca3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K Ca3.1 channel blocker and vasodilator. © 2012 Elsevier Ltd. | * |
dc.language | English | * |
dc.title | Modafinil inhibits K Ca3.1 currents and muscle contraction via a cAMP-dependent mechanism | * |
dc.type | Article | * |
dc.relation.issue | 1 | * |
dc.relation.volume | 66 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 51 | * |
dc.relation.lastpage | 59 | * |
dc.relation.journaltitle | Pharmacological Research | * |
dc.identifier.doi | 10.1016/j.phrs.2012.02.009 | * |
dc.identifier.wosid | WOS:000304569600006 | * |
dc.identifier.scopusid | 2-s2.0-84862828635 | * |
dc.author.google | Choi S. | * |
dc.author.google | Kim M.Y. | * |
dc.author.google | Joo K.Y. | * |
dc.author.google | Park S. | * |
dc.author.google | Kim J.A. | * |
dc.author.google | Jung J.-C. | * |
dc.author.google | Oh S. | * |
dc.author.google | Suh S.H. | * |
dc.contributor.scopusid | 서석효(55666113100) | * |
dc.contributor.scopusid | 오세관(7404103757) | * |
dc.contributor.scopusid | 최신규(12783276200) | * |
dc.contributor.scopusid | 박성희(8848996000) | * |
dc.date.modifydate | 20240220100710 | * |