DYNAMICS OF THE SECRETORY RESPONSE EVOKED BY ENDOTHELIN-1 IN ADRENAL CHROMAFFIN CELLS

Recently, we have observed that endothelin-1 (ET-1) evokes the release of catecholamines (CA) from adrenal chromaffin cells. We have investigated this secretagogue action of ET-1 on cultured adrenal chromaffin cells using a real-time monitoring system. Pulsatile exposure to ET-1 evoked transient secretory responses in a dose-dependent manner, whereas repetitive stimulation produced a rapid tachyphylaxis. This secretagogue activity was dependent on extracellular Ca2+ and was blocked by 85% by 10(-5) M nifedipine. The onset of the secretory response to ET-1 was very slow, and the duration of the response was much longer than that seen with acetylcholine (ACh). These novel dynamics may well be related to the mechanism of action of ET-1 in these cells. In addition, ET-1 produced a synergistic increase in ACh-evoked release, suggesting that ET-1 may physiologically modulate ACh-evoked CA release in adrenal chromaffin cells by a mechanism involving dihydropyridine-sensitive Ca2+ channels.