title: Lysophosphatidylethanolamine increases intracellular Ca(2+) through LPA(1) in PC-12 neuronal cells.
abstract: G protein-coupled receptors (GPCRs) have been implicated in lysophosphatidylethanolamine (LPE)-induced increases in intracellular Ca(2+) ([Ca(2+)]i), but in different cell types, this response may be dependent or independent of lysophosphatidic acid (LPA) GPCR. The effects of LPEs from Grifola frondosa on the neuronal differentiation and apoptosis of PC-12 neuronal cells have been previously reported. In the present study, the authors sought to identify the mechanism responsible for the effects of LPEs in PC-12 neuronal cells. LPE increase [Ca(2+)]i concentration-dependently in PC-12 neuronal cells, but this LPE-induced [Ca(2+)]i increase was less than that elicited by LPA. Studies using specific inhibitors showed that LPE-induced Ca(2+) response was mediated via pertussis toxin-sensitive Gi/o proteins, edelfosine-sensitive phospholipase C, and 2-APB-sensitive IP3 receptor and by Ca(2+) influx across the cell membrane, and that this did not involve the conversion of LPE to LPA. Furthermore, LPE- and LPA-induced responses were found to show homologous and heterologous desensitization in PC-12 cells. VPC32183 and Ki16425 (antagonists of LPA1 and LPA3) inhibited LPE-induced [Ca(2+)]i increases. Furthermore, AM-095 (a specific inhibitor of LPA1) inhibited LPE-induced Ca(2+) response completely in PC-12 cells. These findings indicate LPE increases [Ca(2+)]i via a LPA1/Gi/o proteins/phospholipase C/IP3/Ca(2+) rise/Ca(2+) influx pathway in PC-12 neuronal cells.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), and College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), and College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), and College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea. Electronic address: imds@pusan.ac.kr.
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Im
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; C008301:lysophosphatidylethanolamine; D002118:Calcium
keywords: GPCR; LPA(1); Lysophosphatidic acid; Lysophosphatidylethanolamine; Neuron; Receptor