Ca(2+) channels involved in endothelin-induced mitogenic response in carotid artery vascular smooth muscle cells.
Endothelin (ET)-1 activates two types of Ca(2+)-permeable nonselective cation channels (NSCC-1 and NSCC-2) and a store-operated Ca(2+) channel (SOCC) in rabbit internal carotid artery (ICA) vascular smooth muscle cells (VSMCs) in addition to the voltage-operated Ca(2+) channel (VOCC). These channels can be discriminated using the Ca(2+) channel blockers SK&F-96365 and LOE-908. SK&F-96365 is sensitive to NSCC-2 and SOCC, and LOE-908 is sensitive to NSCC-1 and NSCC-2. On the basis of sensitivity to nifedipine, a specific blocker of the L-type VOCC, VOCCs have a minor role in ET-1-induced mitogenesis. Both LOE-908 and SK&F-96365 inhibited ET-1-induced mitogenesis in a concentration-dependent manner, and the combination of LOE-908 and SK&F-96365 abolished it. The IC(50) values of these blockers for ET-1-induced mitogenesis correlated well with those of the ET-1-induced intracellular free Ca(2+) concentration responses. These results indicate that the inhibitory action of these blockers on ET-1-induced mitogenesis may be mediated by blockade of NSCC-1, NSCC-2, and SOCC. Collectively, extracellular Ca(2+) influx through NSCC-1, NSCC-2, and SOCC may be essential for ET-1-induced mitogenesis in ICA VSMCs.
Kawanabe
Yoshifumi
Y
Department of Neurosurgery, Kyoto University Faculty of Medicine, Kyoto 606-8507, Japan. kawanabe@kuhp.kyoto-u.ac.jp
Hashimoto
Nobuo
N
Masaki
Tomoh
T
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000502:physiology*; D002339:Carotid Arteries / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D004553:Electric Conductivity; D019332:Endothelin-1 / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011817:Rabbits
D000081:Acetamides; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019332:Endothelin-1; D007093:Imidazoles; D007546:Isoquinolines; C081356:LOE 908; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium