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

Abstract

1 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. 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 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. 3 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. 4 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. 5 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. 6 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.