Characterization of Ca2+ influx induced by dimethylphytosphingosine and lysophosphatidylcholine in U937 monocytes.
Calcium is a ubiquitous second messenger controlling a broad range of cellular functions. We previously observed that N,N-dimethyl-D-ribo-phytosphingosine (DMPH) and lysophosphatidylcholine (LPC) induced Ca2+ influx across the plasma membrane in U937 monocytes. In this study, we characterized the Ca2+ influx induced by DMPH and LPC. L-type voltage-gated Ca2+ channel blockers, verapamil and nifedipine, significantly reduced LPC-induced Ca2+ influx, but not DMPH-induced one. On the other hand, non-specific Ca2+ channel blockers, Ga3+ and La3+, considerably reduced DMPH- and LPC-induced Ca2+ influx. Preincubation of the cells with forskolin enhanced DMPH-induced Ca2+ influx, however, LPC-induced Ca2+ influx was not affected by the treatment. The enhancement by forskolin was blocked by KT5720, a PKA inhibitor. We also confirmed the presence of TRPM7 and absence of TRPM3 in U937 cells. Therefore, our characterization of Ca2+ influx in U937 human monocytes shows the presence of two different types of Ca2+ channels modulated by lysolipid molecules, DMPH and LPC. LPC may induce Ca2+ influx via L-type Ca2+ channels and DMPH seems to induce Ca2+ influx through TRPM7 in U937 human monocytes.
Lee
Yun-Kyung
YK
Laboratory of Pharmacology, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 609-735, Republic of Korea.
Im
Young-Jin
YJ
Kim
Yu-Lee
YL
Im
Dong-Soon
DS
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D050053:TRPM Cation Channels / Q000502:physiology; D020298:U937 Cells
D008244:Lysophosphatidylcholines; D050053:TRPM Cation Channels; C012491:phytosphingosine; C061800:N,N-dimethylsphingosine; D013110:Sphingosine; D002118:Calcium