Abstract
Sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) have been reported to activate muscarinic receptor-activated inward rectifier K+ current (I K.ACh) in cultured guinea pig atrial myocytes with similar nanomolar potency. Members of the endothelial differentiation gene (Edg) receptor family were recently identified as receptors for SPP; however, these receptors respond only to micromolar concentrations of SPPC. Here we investigated the sphingolipid-induced activation ofI K.ACh in freshly isolated guinea pig, mouse, and human atrial myocytes. SPP activatedI K.ACh in atrial myocytes from all three species with a similar nanomolar potency (EC50 values: 4–8 nM). At these low concentrations, SPPC also activatedI K.ACh in guinea pig myocytes. In contrast, SPPC was almost ineffective in mouse and human myocytes, thus resembling the pharmacology of the Edg receptors. Transcripts ofEdg-1, Edg-3, and Edg-5were detected in human atrial cells. Moreover, activation ofI K.ACh by SPP was blocked by the Edg-3-selective antagonist suramin, which did not affect basal or carbachol-stimulated K+ currents. In conclusion, these data indicate that I K.ACh activation by SPP and SPPC exhibits large species differences. Furthermore, they suggest that SPP-induced I K.ACh activation in human atrial myocytes is mediated by the Edg-3 subtype of SPP receptors.
Footnotes
- Received December 29, 1999.
- Accepted May 16, 2000.
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Send reprint requests to: Dr. Herbert M. Himmel, Institut für Pharmakologie und Toxikologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Karl-Marx-Straβe 3, D-01109 Dresden, Germany. E-mail: himmel{at}rcs.urz.tu-dresden.de
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↵1 These authors contributed equally to this work.
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This work was supported in part by the Deutsche Forschungsgemeinschaft (Grant ME 1734/1 to D.M.z.H.).
- The American Society for Pharmacology and Experimental Therapeutics
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