Endothelin-1 stimulation of noradrenaline and adrenaline release from adrenal chromaffin cells.
Endothelin-1 (ET-1) stimulated release of both noradrenaline and adrenaline from cultured bovine adrenal chromaffin cells; stimulated release was small compared to that elicited by 50 mM potassium. Sarafotoxin-6b stimulated release to a similar extent as ET-1. The ET-1 stimulated release had an EC50 of about 1 nM. This calcium-dependent release was partially inhibited by nitrendipine (1 microM), but there was no synergistic interaction with the calcium channel agonist BAY K 8644 (1 microM). There was also no synergistic release seen when submaximal stimulation with potassium was combined with ET-1. Stimulation of fura-2 loaded cells with ET-1 produced an unusual timecourse of response which rose slowly to a maximum which was sustained. These results show that ET-1 may stimulate both noradrenaline and adrenaline containing chromaffin cells by a mechanism which, while partially dependent on dihydropyridine sensitive calcium channels, is distinct from the calcium channel agonist or membrane depolarization.
Boarder
M R
MR
Department of Pharmacology and Therapeutics, University of Leicester, U.K.
Marriott
D B
DB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D002417:Cattle; D002837:Chromaffin Granules / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D004837:Epinephrine / Q000378:metabolism*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D014757:Viper Venoms / Q000494:pharmacology
D015220:Calcium Channels; D016232:Endothelins; D014757:Viper Venoms; C057354:sarafotoxins s6; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine