title: Pharmacological characterization of receptor-mediated Ca2+ entry in endothelin-1-induced catecholamine release from cultured bovine adrenal chromaffin cells.
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 Ca2+, blockers of L-, N-, P- and Q-types of voltage-operated Ca2+ channels (VOCC) such as nifedipine (L-type), omega-conotoxin GVIA (N-type), omega-agatoxin IVA (P-type) and omega-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), and 45Ca2+ uptake in cultured bovine adrenal chromaffin cells. ET-1 but not ET-3 induced increases in release of catecholamines, [Ca2+]i, and 45Ca2+ uptake. The responses to ET-1 were abolished by the antagonist for ET(A) receptors, BQ-123, but not by the antagonist for ET(B) 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 omega-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 ET(A) 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.
authors.affiliation: Department of Physiology, Gifu University School of Medicine, Japan. kl&commat;cc.gifu-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamuro
authors.forename: X F
authors.initials: XF
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Furutani
authors.forename: S
authors.initials: S
authors.lastname: Miwa
authors.forename: T
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000311:Adrenal Glands; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D004837:Epinephrine / Q000096:biosynthesis / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D016014:Linear Models; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D000081:Acetamides; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D007093:Imidazoles; D007473:Ion Channels; D007546:Isoquinolines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C081356:LOE 908; D020866:omega-Conotoxin GVIA; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine