Ouabain augments and maintains the catecholamine release responses evoked by repetitive pulses of potassium, caffeine or histamine in perifused bovine chromaffin cells

Cardiac glycosides such as ouabain augment the release of neurotransmitters and hormones from various organs, tissues and cell systems. Here we have investigated novel aspects of the ouabain effects on fast-perifused bovine adrenal chromaffin cells subjected to repetitive stimulation during long-time periods with secretagogues that enhance Ca2+ entry (i.e. 100 mM K+solution) or causing the release into the cytosol of the Ca2+ stored in the endoplasmic reticulum (i.e. 20 mM caffeine or 100 μM histamine). After 1 h of intermittent stimulation, the amperometrically measured catecholamine release responses decayed to 50% with K+ pulses, and to 10–15% with caffeine or histamine pulses. Ouabain (10 μM) augmented 2-fold the K+ secretory responses and kept them high, along an hour. When given after the responses had decayed upon repetitive caffeine or histamine pulsing, ouabain gradually restored such responses to their initial control values. On the basis of these results, we raise the hypothesis that ouabain may facilitate the handling by the cell of the endoplasmic reticulum Ca2+ fluxes that are known to be involved in secretory vesicle transport and the regulation of exocytosis. This may have physiological and pathological interest in the light of an endogenous ouabain steroid found in the adrenal cortex.