title: Failure of endothelin-1 to activate store-operated Ca2+ channels by lack of mobilization from intracellular Ca2+ stores in cultured bovine adrenal chromaffin cells.
abstract: We have recently shown that in addition to L-type voltage-operated Ca2+ channel (VOC), endothelin-1 (ET-1) stimulation opens two types of Ca2+-permeable nonselective cation channels [designated nonselective cation channel-1 (NSCC-1) and NSCC-2]. However, in this Ca2+ entry, the involvement of store-operated Ca2+ channel (SOCC), which is suggested to exist in chromaffin cells, was unclear. Those NSCCs as well as SOCC can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. To clarify whether SOCC should actually exist and play a role in Ca2+ entry in chromaffin cells stimulated with ET-1, we examined the effects of removal of extracellular Ca2+, thapsigargin (TG, an inhibitor of endoplasmic reticulum Ca2+-ATPase), LOE 908 and SK&F 96365 on cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured bovine adrenal chromaffin cells. After the cells were exposed to Ca2+-free medium followed by exposure to TG to deplete Ca2+ from the intracellular Ca2+ store, restoration of extracellular Ca2+ caused a gradual increase in [Ca2+]i (to about 200% of control). The increase was unaffected by LOE 908, but completely abolished by SK&F 96365. In the Ca2+-free medium, no increase in [Ca2+]i by ET-1 was observed, but the subsequent restoration of extracellular Ca2+ induced a rapid increase in [Ca2+]i (to the same level of [Ca2+]i as that evoked by ET-1 in the normal medium (1.0 mM Ca2+)). Since SK&F 96365 is also a blocker of SOCC, these results indicate that in bovine adrenal chromaffin cells, Ca2+ entry through SOCC (Ca2+ influx through the capacitative Ca2+ entry system) occurs but is comparably weak, and that it virtually does not work on the stimulation of ET-1.
authors.affiliation: Department of Physiology, Gifu University School of Medicine, Japan. kl@cc.gifu-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamuro
authors.forename: X F
authors.initials: XF
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Miwa
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000081:Acetamides; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007473:Ion Channels; D007546:Isoquinolines; C081356:LOE 908; D019284:Thapsigargin; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium