title: Positive and negative controls by protein kinases of sodium-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells stimulated by lysophosphatidic acid.
abstract: We previously found that lysophosphatidic acid (LPA), a bioactive phospholipid, induced Na+-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells, possibly by activating a Na+/Ca2+ exchanger. The present study on the structure-activity relationship of its action revealed that 1-acyl type LPAs were stronger stimulants than the corresponding 1-O-alkyl type LPAs having a long alkyl moiety with the same chain length. Lysophosphatidylglycerol, suramin and N-palmitoyl-tyrosine phosphoric acid have all been reported to inhibit the action of LPA in some animal cells and platelets, but only lysophosphatidylglycerol was found to inhibit selectively LPA-induced Ca2+ efflux from chromaffin cells. LPA-induced Ca2+ extrusion was suggested to be involved in both acceleration of return of intracellular Ca2+ in Fura 2-loaded bovine chromaffin cells after addition of carbachol, and inhibition of carbachol-induced catecholamine release when the cells were co-incubated with LPA. The Ca2+ efflux from chromaffin cells stimulated by LPA was augmented by their pretreatment with staurosporine or calphostin C, inhibitors of protein kinase C, but reduced by their preincubation with phorbol 12-myristate 13-acetate. Furthermore, the response to LPA was potentiated by sodium vanadate, a protein tyrosine phosphatase inhibitor, but inhibited by genistein, an inhibitor of protein tyrosine kinase. These results suggest that protein kinase C and protein tyrosine kinase are involved negatively and positively, respectively, in the signal transduction triggered by LPA, leading to activation of the Na+/Ca2+ exchanger.
authors.affiliation: Department of Health Chemistry, Faculty of Pharmaceutical Sciences, The University of Tokushima, Japan. tokumura@ph.tokushima-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Tokumura
authors.forename: M
authors.initials: M
authors.lastname: Okuno
authors.forename: K
authors.initials: K
authors.lastname: Fukuzawa
authors.forename: H
authors.initials: H
authors.lastname: Houchi
authors.forename: K
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Oka
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013498:Suramin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D019831:Sodium-Calcium Exchanger; D014638:Vanadates; D013498:Suramin; D002217:Carbachol; D012964:Sodium; D019833:Genistein; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium