Correlation between catecholamine release and sodium pump inhibition in the perfused adrenal gland of the cat

1 Ca(2+) reintroduction to retrogradely perfused and ouabain (10(-4) M)-treated cat adrenal glands caused a catecholamine secretory response which was greater the longer the time of exposure to the cardiac glycoside. Such a response was proportional to the external Na(+) concentration [Na(+)](o).2 A qualitatively similar, yet smaller response was observed when glands were perfused with Krebs solution lacking K(+) ions; thus, K(+) deprivation mimicked the secretory effects of ouabain. Catecholamine secretion evoked by Ca(2+) reintroduction in K(+)-free solution (0-K(+)) was also proportional to [Na(+)](o) and greater the longer the time of exposure of the gland to 0-K(+) solution.3 The ionophore X537A also mimicked the ouabain effects, since Ca(2+) reintroduction to glands treated with this agent (25 muM) caused a sharp secretory response. When added together with X537A, ouabain (10(-4) M) did not modify the response to the ionophore.4 N-ethylmaleimide (NEM), another Na(+), K(+)-ATPase inhibitor, did not evoke the release of catecholamines; on the contrary, NEM (10(-4) M) inhibited the catecholamine secretory response to high [K(+)](o), acetylcholine, Ca(2+) reintroduction and ouabain.5 Ouabain (10(-4) M) inhibited the uptake of (86)Rb into adreno-medullary tissue by 60%. Maximal inhibition had already occurred 2 min after adding the drug, indicating a lack of temporal correlation between ATPase inhibition and the ouabain secretory response, which took longer (about 30-40 min) to reach its peak. NEM (10(-4) M) blocked (86)Rb uptake in a similar manner.6 The results are further evidence in favour of the presence of a Na(+)-Ca(2+) exchange system in the chromaffin cell membrane, probably involved in the control of [Ca(2+)](i) and in the modulation of catecholamine secretion. This system is activated by increasing [Na(+)](i), either directly (ionophore X537A, increased [Na(+)](o)) or indirectly (Na(+) pump inhibition). However, the simple inhibition of Na(+) pumping does not always lead to a catecholamine secretory response; such is the case for NEM.