Endothelin-1-induced contraction of rat thoracic aorta depends on calcium entry through three types of calcium channel.
We have recently shown that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1-H-imidazoe l hydrochloride (SK&F 96365) (a blocker of NSCC-2 and SOCC) and (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma l)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]acetamide (LOE 908) (a blocker of NSCC-1 and NSCC-2). For our study we characterized Ca2+ channels involved in ET-1-induced contractions and increases in the intracellular free Ca2+ concentration ([Ca2+]i) using these blockers. Our results show that the response to lower concentrations of ET-1 involves only one Ca2+ channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2). In contrast, the response to higher concentrations of ET-1 involves two types of Ca2+ channel in addition to NSCC-2: one is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC), and the other is resistant to SK&F 96365 but sensitive to LOE 908 (NSCC-1). Furthermore, the percentage contribution of Ca2+ entry through NSCC-1, NSCC-2 and SOCC is calculated to be 10%, 50-60% and 30-40%, respectively.
Zhang
X F
XF
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Iwamuro
Y
Y
Okamoto
Y
Y
Kawanabe
Y
Y
Masaki
T
T
Miwa
S
S
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
D000081:Acetamides; 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