RT Journal Article
SR Electronic
T1 Evidence for Edg-3 Receptor-Mediated Activation of<em>I</em>
<sub>K.ACh</sub> by Sphingosine-1-Phosphate in Human Atrial Cardiomyocytes
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 449
OP 454
DO 10.1124/mol.58.2.449
VO 58
IS 2
A1 Herbert M. Himmel
A1 Dagmar Meyer zu Heringdorf
A1 Eva Graf
A1 Dobromir Dobrev
A1 Ariane Kortner
A1 Stephan Schüler
A1 Karl H. Jakobs
A1 Ursula Ravens
YR 2000
UL http://molpharm.aspetjournals.org/content/58/2/449.abstract
AB 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.