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- Author
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Lee, K., Morita, H., Iwamuro, Y., Zhang, X.-F., Okamoto, Y., Nakagawa, T., Hasegawa, H., Furutani, H., Miwa, S., and Masaki, T.
- Abstract
To clarify the mechanism for the endothelin-1 (ET-1)-induced release of catecholamines from the adrenal gland, we examined the effects of removal of extracellular Ca
2+ , blockers of L-, N-, P- and Q-types of voltage-operated Ca2+ channels (VOCC) such as nifedipine (L-type), ω-conotoxin GVIA (N-type), ω-agatoxin IVA (P-type) and ω-conotoxin MVIIC (Q-type) and blockers of voltage-independent Ca2+ entry channel such as SK&F 96365 and LOE 908 on release of catecholamines, the cytosolic free Ca2+ concentration ([Ca2+ ]i ), and45 Ca2+ uptake in cultured bovine adrenal chromaffin cells. ET-1 but not ET-3 induced increases in release of catecholamines, [Ca2+ ]i , and45 Ca2+ uptake. The responses to ET-1 were abolished by the antagonist for ETA receptors, BQ-123, but not by the antagonist for ETB receptors, BQ-788, and they were abolished by removal of extracellular Ca2+ . The increases were only partially inhibited (to about 65% of control) by nifedipine but unaffected by any of the ω-toxins. The nifedipine-resistant increase was inhibited by SK&F 96365 (to about 40%) and abolished by LOE 908 alone. These results indicate that ET-1 augments the release of catecholamines from adrenal chromaffin cells through ETA receptors, by activating two types of Ca2+ entry channels in addition to L-type VOCC: one (nonselective cation channel-1; NSCC-1) is sensitive to LOE 908 but resistant to SK&F 96365, whereas the other (NSCC-2) is sensitive to both LOE 908 and SK&F 96365. [ABSTRACT FROM AUTHOR]- Published
- 1999
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