Characterization of Ca(2+) channels involved in endothelin-1-induced mitogenic responses in vascular smooth muscle cells.
Ca(2+) channels involved in the endothelin-1-induced mitogenic response of cultured rat thoracic aorta smooth muscle cells, A7r5 cells, were characterized using the Ca(2+) channel blockers, LOE 908 and SK&F 96365. Stimulation of A7r5 cells with endothelin-1 induced a mitogenic response as well as a biphasic increase in the intracellular-free Ca(2+) concentration. Based on the sensitivity to nifedipine, a specific blocker of L-type voltage-operated Ca(2+) channel (VOCC), Ca(2+) influx through VOCC has a minor role in endothelin-1-induced mitogenic responses. On the other hand, Ca(2+) influx through voltage-independent Ca(2+) channels (VICCs) plays an important part in endothelin-1-induced mitogenesis. Moreover, based on their sensitivity to SK&F 96365 and LOE 908, VICCs consist of two types of Ca(2+)-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca(2+) channel (SOCC). Ca(2+) influx through NSCC-1, NSCC-2 and SOCC contributes to 35%, 30% and 35%, respectively, to the nifedipine-resistant component of the endothelin-1 mitogenic response.
Kawanabe
Y
Y
Department of Neurosurgery, Faculty of Medicine, Kyoto University, Kyoto, Japan. kawanabe@kuhp.kyoto-u.ac.jp
Okamoto
Y
Y
Hashimoto
N
N
Masaki
T
T
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D013997:Time Factors
D000081:Acetamides; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019332:Endothelin-1; D007093:Imidazoles; D007546:Isoquinolines; C081356:LOE 908; D004247:DNA; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium