Ca(2+) channels activated by endothelin-1 in CHO cells expressing endothelin-A or endothelin-B receptors.
We compared the Ca(2+) channels activated by endothelin-1 (ET-1) in Chinese hamster ovary (CHO) cells stably expressing endothelin type A (ET(A)) or endothelin type B (ET(B)) receptors using the Ca(2+) channel blockers LOE-908 and SK&F-96365. In both CHO-ET(A) and CHO-ET(B), ET-1 at 0.1 nM activated the Ca(2+)-permeable nonselective cation channel-1 (NSCC-1), which was sensitive to LOE-908 and resistant to SK&F-96365. ET-1 at 1 nM activated NSCC-2 in addition to NSCC-1; NSCC-2 was sensitive to both LOE-908 and SK&F-96365. ET-1 at 10 nM activated the same channels as 1 nM ET-1 in both cell types, but in CHO-ET(A), it additionally activated the store-operated Ca(2+) channel (SOCC), which was resistant to LOE-908 and sensitive to SK&F-96365. Up to 1 nM ET-1, the level of the formation of inositol phosphates (IPs) was low and similar in both cell types, but, at 10 nM ET-1, it was far greater in CHO-ET(A) than in CHO-ET(B). These results show that, in CHO-ET(A) and CHO-ET(B), ET-1 up to 10 nM activated the same Ca(2+) entry channels: 0.1 nM ET-1 activated NSCC-1, and ET-1 > or = 1 nM activated NSCC-1 and NSCC-2. Notably, in CHO-ET(A), 10 nM ET-1 activated SOCCs because of the higher formation of IPs.
Kawanabe
Y
Y
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8507, Japan. kawanabe@kuhp.kyoto-u.ac.jp
Okamoto
Y
Y
Enoki
T
T
Hashimoto
N
N
Masaki
T
T
D000081:Acetamides / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D016466:CHO Cells; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004594:Electrophysiology; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D007546:Isoquinolines / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
D000081:Acetamides; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007295:Inositol Phosphates; D007546:Isoquinolines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C081356:LOE 908; D019284:Thapsigargin; D000251:Adenosine Triphosphatases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole