Lysophosphatidylcholine transduces Ca2+ signaling via the platelet-activating factor receptor in macrophages.
To clarify the molecular mechanism underlying the lysophosphatidylcholine (LPC) signaling, we studied the effect of LPC on the intracellular free calcium concentration ([Ca2+]i) in murine peritoneal macrophages. LPC when added alone induced biphasic elevation of [Ca2+]i, which consisted of a rapid increase followed by sustained elevation. LPC, when added with equimolar cholesterol, induced only the rapid increase in [Ca2+]i, which was blocked by WEB-2086, a selective platelet-activating factor (PAF) receptor antagonist. These results suggest LPC exerts a specific Ca2+ signaling. The sustained elevation reflected the cell lysis. Furthermore, we confirmed its pathway in a more specific manner using cloned PAF receptors expressed in Chinese hamster ovary cells. LPC induced an elevation of [Ca2+]i in a concentration-dependent manner only when the PAF receptor had been expressed, and the elevation of [Ca2+]i was blocked by WEB-2086. Taken together, LPC transduces Ca2+ signaling via the PAF receptor. Activation of the PAF receptor by LPC may indicate its novel important role in the pathogenesis of atherosclerosis.
Ogita
T
T
Fourth Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Tanaka
Y
Y
Nakaoka
T
T
Matsuoka
R
R
Kira
Y
Y
Nakamura
M
M
Shimizu
T
T
Fujita
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D016466:CHO Cells / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002784:Cholesterol / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009994:Osmolar Concentration; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D008244:Lysophosphatidylcholines; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; D002118:Calcium