CORRELATION BETWEEN CATECHOLAMINE RELEASE AND SODIUM PUMP INHIBITION IN THE PERFUSED ADRENAL GLAND OF THE CAT

Ca2+ re introduction to retrogradely perfused and ouabain (10−4M)‐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+]0. 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 Ca2+ reintroduction in K+‐free solution (0‐K+) was also proportional to [Na+]0 and greater the longer the time of exposure of the gland to 0‐K+ solution. The ionophore X537A also mimicked the ouabain effects, since Ca2+ reintroduction to glands treated with this agent (25 μm) caused a sharp secretory response. When added together with X537A, ouabain (10−4m) did not modify the response to the ionophore. N‐ethylmaleimide (NEM), another Na+, K+‐ATPase inhibitor, did not evoke the release of catecholamines; on the contrary, NEM (10−4m) inhibited the catecholamine secretory response to high [K+]0, acetylcholine, Ca2+ reintroduction and ouabain. Ouabain (10−4 m) inhibited the uptake of 86Rb 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 86Rb uptake in a similar manner. The results are further evidence in favour of the presence of a Na+‐Ca2+ exchange system in the chromaffin cell membrane, probably involved in the control of [Ca2+]i, and in the modulation of catecholamine secretion. This system is activated by increasing [Na+]i, either directly (ionophore X537A, increased [Na+]0) 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.