title: Effects of calcium, calmodulin, protein kinase C and protein tyrosine kinases on volume-activated taurine efflux in human erythroleukemia cells.
abstract: The effects of calcium, calmodulin, protein kinase C (PKC) and protein tyrosine kinase (PTK) modulators were examined on the volume-activated taurine efflux in the erythroleukemia cell line K562. Exposure to hypoosmotic solution significantly increased taurine efflux and intracellular calcium concentration ([Ca2+]i). The Ca2+ channel blockers La3+ (1 mM), verapamil (200 microM) and nifedipine (100 microM) inhibited the hypoosmotically-induced [Ca2+]i increase by more than 90%, while the volume-activated taurine efflux was inhibited by 61.3 +/- 9.5, 74.1 +/- 9.3 and 38.0 +/- 1.5%, respectively. Furthermore, the calmodulin inhibitors W7 (50 microM) and trifluoperazine (10 microM) and the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62 (2 microM) significantly blocked the volume-activated taurine efflux by 93.4 +/- 2.7, 77.9 +/- 3.5 and 61.3 +/- 15.8%, respectively. In contrast, the PKC inhibitor staurosporine (200 nM) or the PKC activator phorbol 12-myristate 13-acetate (100 nM) did not have significant effects on the volume-activated taurine efflux. However, pretreatment with PTK inhibitors genistein, tyrphostin A25, and tyrphostin A47 blocked the volume-activated taurine efflux. These results suggest that the volume-activated taurine efflux in K562 cells may not directly involve Ca2+, but may require the presence of calmodulin and/or PTK.
authors.affiliation: Department of Physiology, Chung Shan Medical and Dental College, Taichung, Taiwan ROC. huangcc@mercury.csmc.edu.tw
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: C B
authors.initials: CB
authors.lastname: Chang
authors.forename: J Y
authors.initials: JY
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Basavappa
authors.forename: P H
authors.initials: PH
authors.lastname: Lim
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D048429:Cell Size; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007038:Hypotonic Solutions; D020014:K562 Cells; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013654:Taurine / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002147:Calmodulin; D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D013449:Sulfonamides; D013654:Taurine; D014268:Trifluoperazine; C063302:KN 62; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium