Analysis of Ca2+ entry channels in endothelin-1-induced contraction of rat aorta using new blockers

• Published in: Nihon yakurigaku zasshi Vol. 114 Suppl 1; p. 103P
• Main Authors: Zhang, X F, Iwamuro, Y, Okamoto, Y, Miwa, S, Masaki, T
• Format: Journal Article
• Language: Japanese
• Published: Japan 1999
• Subjects: Acetamides - pharmacology; Animals; Aorta, Thoracic; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels - physiology; Endothelin-1 - physiology; Imidazoles - pharmacology; In Vitro Techniques; Isoquinolines - pharmacology; Nifedipine - pharmacology; Rats; Vasoconstriction - drug effects
• ISSN: 0015-5691
• DOI: 10.1254/fpj.114.supplement_103

1) We have recently shown that endothelin-1 (ET-1) activates two types of Ca(2+)-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. Here we characterized Ca2+ entry channels involved in ET-1-induced contractions of rat thoracic aortic rings and increases in the intracellular free Ca2+ concentration ([Ca2+]i) of single smooth muscle cells using these blockers. 2) LOE 908 or a blocker of voltage-operated Ca2+ channel nifedipine had no effect on the contractions and increases in [Ca2+]i induced by thapsigargin, whereas SK&F 96365 abolished them. 3) The contractions and increases in [Ca2+]i induced by ET-1 depended on extracellular Ca2+ but were resistant to nifedipine. The responses to lower concentrations (< or = 0.1 nM) of ET-1 were abolished by either SK&F 96365 or LOE 908. The responses to higher concentrations (> or = 1 nM) were abolished by SK&F 96365, but were partially resistant to LOE 908. 4) These results show that the contractions and increases in [Ca2+]i of rat aortic smooth muscles at lower concentrations of ET-1 involve only one Ca2+ entry channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those at higher concentrations of ET-1 involve another Ca2+ entry channel which is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC) in addition to the former channel.