Low concentrations of sphingosylphosphorylcholine enhance pulmonary artery vasoreactivity - The role of protein kinase C delta and Ca2+ entry

V A Snetkov, G D Thomas, B Teague, R M Leach, Y Shaifta, G A Knock, P I Aaronson, J P T Ward

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Sphingosylphosphorylcholine ( SPC) is a powerful vasoconstrictor, but in vitro its EC50 is approximate to 100-fold more than plasma concentrations. We examined whether subcontractile concentrations of SPC ( 100 nmol/ L of SPC, and independent of the endothelium, 2-aminoethoxydiphenylborane-sensitive Ca2+ entry, and Rho kinase. It was abolished by the phospholipase C inhibitor U73122, the broad spectrum protein kinase C ( PKC) inhibitor Ro31-8220, and the PKC delta inhibitor rottlerin, but not by Go6976, which is ineffective against PKC delta. The potentiation could be attributed to enhancement of Ca2+ entry. SPC also potentiated the responses to prostaglandin F-2 alpha and U436619, which activate a 2-aminoethoxydiphenylborane sensitive nonselective cation channel in intrapulmonary arteries. In this case, potentiation was partially inhibited by diltiazem but abolished by 2-aminoethoxydiphenylborane, Ro31- 8220, and rottlerin. SPC ( 1 mu mol/ L) caused translocation of PKC delta to the perinuclear region and cytoskeleton of cultured intrapulmonary artery smooth muscle cells. We present the novel finding that low, subcontractile concentrations of SPC potentiate Ca2+ entry in intrapulmonary arteries through both voltage-dependent and independent pathways via a receptor-dependent mechanism involving PKC delta. This has implications for the physiological role of SPC, especially in cardiovascular disease, where SPC is reported to be elevated
Original languageEnglish
Pages (from-to)239 - 245
Number of pages7
JournalHypertension
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Dive into the research topics of 'Low concentrations of sphingosylphosphorylcholine enhance pulmonary artery vasoreactivity - The role of protein kinase C delta and Ca2+ entry'. Together they form a unique fingerprint.

Cite this