PMID- 12433841
OWN - NLM
STAT- MEDLINE
DCOM- 20021205
LR  - 20211203
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 91
IP  - 10
DP  - 2002 Nov 15
TI  - Involvement of Src family protein tyrosine kinases in Ca(2+) sensitization of 
      coronary artery contraction mediated by a sphingosylphosphorylcholine-Rho-kinase 
      pathway.
PG  - 953-60
AB  - We recently reported that sphingosylphosphorylcholine (SPC) is a novel messenger 
      for Rho-kinase-mediated Ca(2+) sensitization of vascular smooth muscle (VSM) 
      contraction. Subcellular localization and kinase activity of Src family protein 
      kinases (SrcPTKs), except for c-Src, is controlled by a reversible 
      S-palmitoylation, an event inhibited by eicosapentaenoic acid (EPA). We examined 
      the possible involvement of SrcPTKs in SPC-induced Ca(2+) sensitization and 
      effects of EPA. We used porcine coronary VSM and rat aortic VSM cells (VSMCs) in 
      primary culture. An SrcPTKs inhibitor, PP1, and EPA inhibited SPC-induced 
      contraction, concentration-dependently, without affecting [Ca(2+)](i) levels and 
      the Ca(2+)-dependent contraction induced by high K(+) depolarization. A digitized 
      immunocytochemical analysis in VSMCs revealed that SPC induced translocation of 
      Fyn, but not of c-Src, from the cytosol to the cell membrane, an event abolished 
      by EPA. Translocation of Rho-kinase from the cytosol to the cell membrane by SPC 
      was also inhibited by EPA and PP1. The SPC-induced activation of SrcPTKs was 
      blocked by EPA and PP1, but not by Y27632, an Rho-kinase inhibitor. 
      Rho-kinase-dependent phosphorylation of myosin phosphatase induced by SPC was 
      inhibited by EPA, PP1, and Y27632. Translocation and activation of SrcPTKs, 
      including Fyn, play an important role in Ca(2+) sensitization of VSM contractions 
      mediated by a SPC-Rho-kinase pathway.
FAU - Nakao, Fumiaki
AU  - Nakao F
AD  - Department of Cardiovascular Medicine, Yamaguchi University School of Medicine, 
      Yamaguchi, Japan.
FAU - Kobayashi, Sei
AU  - Kobayashi S
FAU - Mogami, Kimiko
AU  - Mogami K
FAU - Mizukami, Yoichi
AU  - Mizukami Y
FAU - Shirao, Satoshi
AU  - Shirao S
FAU - Miwa, Saori
AU  - Miwa S
FAU - Todoroki-Ikeda, Natsuko
AU  - Todoroki-Ikeda N
FAU - Ito, Masaaki
AU  - Ito M
FAU - Matsuzaki, Masunori
AU  - Matsuzaki M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Palmitates)
RN  - 10216-23-6 (sphingosine phosphorylcholine)
RN  - 107-73-3 (Phosphorylcholine)
RN  - 18263-25-7 (2-bromopalmitate)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - NGZ37HRE42 (Sphingosine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Acylation/drug effects
MH  - Animals
MH  - Blotting, Western
MH  - Calcium/*metabolism
MH  - Coronary Vessels/*physiology
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Intracellular Signaling Peptides and Proteins
MH  - Isometric Contraction/drug effects/physiology
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/drug effects/physiology
MH  - Palmitates/pharmacology
MH  - Phosphorylcholine/*analogs & derivatives/*metabolism/pharmacology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Protein Transport/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Second Messenger Systems/physiology
MH  - Signal Transduction/drug effects/physiology
MH  - Sphingosine/*analogs & derivatives/*metabolism/pharmacology
MH  - Swine
MH  - Vasoconstriction/drug effects/*physiology
MH  - rho-Associated Kinases
MH  - src-Family Kinases/antagonists & inhibitors/*metabolism
EDAT- 2002/11/16 04:00
MHDA- 2002/12/06 04:00
CRDT- 2002/11/16 04:00
PHST- 2002/11/16 04:00 [pubmed]
PHST- 2002/12/06 04:00 [medline]
PHST- 2002/11/16 04:00 [entrez]
AID - 10.1161/01.res.0000042702.04920.bf [doi]
PST - ppublish
SO  - Circ Res. 2002 Nov 15;91(10):953-60. doi: 10.1161/01.res.0000042702.04920.bf.