A NOVEL MEMBRANE-RECEPTOR WITH HIGH-AFFINITY FOR LYSOSPHINGOMYELIN AND SPHINGOSINE 1-PHOSPHATE IN ATRIAL MYOCYTES

Citation
M. Bunemann et al., A NOVEL MEMBRANE-RECEPTOR WITH HIGH-AFFINITY FOR LYSOSPHINGOMYELIN AND SPHINGOSINE 1-PHOSPHATE IN ATRIAL MYOCYTES, EMBO journal, 15(20), 1996, pp. 5527-5534
Citations number
43
Categorie Soggetti
Biology,"Cell Biology
Journal title
ISSN journal
02614189
Volume
15
Issue
20
Year of publication
1996
Pages
5527 - 5534
Database
ISI
SICI code
0261-4189(1996)15:20<5527:ANMWHF>2.0.ZU;2-F
Abstract
Activation of I-K(ACh) is the major effect of the vagal neurotransmitt er acetylcholine in the heart, We report that both lysosphingomyelin ( D-erythro-sphingosyl-phosphorylcholine; SPC) and sphingosine 1-phospha te (SPP) activate I-K(ACh) in guinea pig atrial myocytes through the s ame receptor with an EC(50) of 1.5 and 1.2 nM, respectively. Pertussis toxin abolished the activation of I-K(ACh) by either lipid, The putat ive receptor showed an exquisite stereoselectivity for the naturally o ccurring D-erythro-(2S,3R)-SPC stereoisomer, the structure of which wa s confirmed by mass spectroscopy and NMR, These lipids caused complete homologous and heterologous desensitization with each other but not w ith ACh, indicating that both act on the same receptor. This receptor displays a distinct structure-activity relationship: it requires an un substituted amino group because N-acetyl-SPC, lysophosphatidic acid an d lysophosphatidylcholine were inactive, Because SPP and SPC are natur ally occurring products of membrane lipid metabolism, it appears that these compounds might be important extracellular mediators acting on a family of bona fide G protein-coupled receptors, Expression of these receptors in the heart raises the possibility that sphingolipids may b e a part of the physiological and/or pathophysiological regulation of the heart. Based on their ligand selectivity we propose a classificati on of the sphingolipid receptors.