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-mu-M), but there was no synergistic interaction with the calcium channel agonist BAY K 8644 (1-mu-M). 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.