title: Neuromedin S increases L-type Ca(2+) channel currents through G(i)α-protein and phospholipase C-dependent novel protein kinase C delta pathway in adult rat ventricular myocytes.
abstract: Neuromedin S (NMS), a peptide structurally related to NMU, has been identified in the mammalian heart tissues. However to date, any role of NMS in cardiomyocytes and the relevant mechanisms still remain unknown. In this study, we identified a novel functional role of NMS in modulating L-type Ca(2+) channels in adult rat ventricular myocytes, in which NMU type 2 receptors (NMUR2), but not NMUR1, are endogenously expressed. We found that NMS at 0.1 µM reversibly increased I(Ba) by ~29.7%. Intracellular infusion of GDP-β-S or a selective antibody raised against the G(i)-protein blocked the stimulatory effects of NMS. The classical and novel protein kinase C (nPKC) antagonist calphostin C or chelerythrine chloride, as well as the phospholipase C (PLC) inhibitor U73122, abolished NMS responses, whereas a classical PKC antagonist Gö6976 or a PKA antagonist PKI 5-24 had no such effects. Pretreatment of cells with PKC-δ specific inhibitor rottlerin or intracellular application of a PKC-δ-derived inhibitory peptide, δV1-1, abolished NMS responses, while an inactive control peptide had no effects. In summary, NMS acting through NMUR2 increases I(Ba) via a G(i)α-protein-dependent PKC-δ pathway in rat ventricular myocytes.
authors: Department of Cardiology, Suzhou Kowloon Hospital Shanghai Jiaotong University Medical School, Suzhou, PR China. chenrunxiang1609@yahoo.com.cn
authors: Run-Xiang
authors: RX
authors: Chen
authors: Feng
authors: F
authors: Liu
authors: Yong
authors: Y
authors: Li
authors: Guang-An
authors: GA
authors: Liu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D004963:Estrenes / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D053119:Benzophenanthridines; D001578:Benzopyrans; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D004963:Estrenes; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D011760:Pyrrolidinones; D017981:Receptors, Neurotransmitter; C477270:Ser-Phe-Asn-Ser-Tyr-Glu-Leu-Gly-Glu-Ser-Leu; C497950:neuromedin S; C082444:neuromedin U receptor; C518603:protein kinase inhibitor peptide (5-24); C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C081021:Go 6976; C085746:rottlerin; C016299:chelerythrine; D051745:Protein Kinase C-delta; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go