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Comparison of contractile mechanisms of sphingosylphosphorylcholine and sphingosine-1-phosphate in rabbit coronary artery

Authors
 Soo-Kyoung Choi  ;  Duck-Sun Ahn  ;  Young-Ho Lee 
Citation
 Cardiovascular Research, Vol.82(2) : 324-332, 2009 
Journal Title
 Cardiovascular Research 
ISSN
 0008-6363 
Issue Date
2009
MeSH
Animals ; Calcium/metabolism ; Coronary Vessels/cytology ; Coronary Vessels/drug effects ; Coronary Vessels/metabolism* ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Indoles/pharmacology ; Lysophospholipids/metabolism ; Lysophospholipids/pharmacology* ; Muscle Contraction/drug effects* ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism* ; Myosin-Light-Chain Phosphatase/metabolism ; Phosphorylation ; Phosphorylcholine/analogs & derivatives* ; Phosphorylcholine/metabolism ; Phosphorylcholine/pharmacology ; Rabbits ; Sarcoplasmic Reticulum/metabolism ; Signal Transduction/physiology* ; Sphingosine/analogs & derivatives* ; Sphingosine/metabolism ; Sphingosine/pharmacology ; rho-Associated Kinases/metabolism
Keywords
Sphingosylphosphorylcholine ; Sphingosine-1-phosphate ; [Ca2+]I ; RhoA/RhoA-associated kinase ; Rabbit coronary artery
Abstract
AIMS: Although stimulation with sphingosylphosphorylcholine (SPC) or sphingosine-1-phosphate (S1P) generally leads to similar vascular responses, the contractile patterns and their underlying signalling mechanisms are often distinct. We investigated the different reliance upon Ca2+-dependent and Ca2+-sensitizing mechanisms of constriction in response to SPC or S1P in coronary arteries. METHODS AND RESULTS: Contractile responses, changes in [Ca2+]i, and phosphorylation of myosin light chain phosphatase-targeting subunit (MYPT1) were measured. SPC induced a concentration-dependent sustained contraction. S1P evoked a rapid rise in force (initial transient), which was followed by a secondary sustained force. In the absence of extracellular Ca2+, the concentration dependency of constriction to SPC was shifted to the right, but with no change in maximum force, whereas S1P-induced contraction was significantly blunted. Cyclopiazonic acid (CPA) significantly decreased the initial transient force induced by S1P. In isolated single cells, S1P markedly increased [Ca2+]i, whereas only a modest elevation was noted with SPC. The S1P-induced elevation of [Ca2+]i was abolished by pre-treatment with CPA and was significantly reduced in the absence of extracellular Ca2+. In beta-escin-permeabilized strips, SPC augmented pCa 6.3-induced force; this was significantly inhibited by fasudil hydrochloride. S1P induced little or no augmentation of pCa 6.3-induced force. In intact arteries, SPC-induced contraction was completely inhibited by fasudil hydrochloride. Fasudil hydrochloride had no effect on the initial transient force induced by S1P but significantly inhibited the secondary sustained force. SPC induced a several-fold increase in Thr696 and Thr853 phosphorylation of MYPT1, but S1P did not affect phosphorylation of MYPT1. CONCLUSION: Our results suggest that constriction of coronary arteries in response to the bioactive lipid S1P or SPC occurs by distinct signalling pathways. Activation of the RhoA/RhoA-associated kinase pathway and subsequent phosphorylation of MYPT1 play a key role in SPC-induced coronary contraction, whereas elevation of [Ca2+]i is crucial for S1P-induced coronary constriction.
Files in This Item:
T200900984.pdf Download
DOI
10.1093/cvr/cvp054
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
Choi, Soo Kyoung(최수경) ORCID logo https://orcid.org/0000-0002-7115-6358
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103745
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