The role of energy metabolism in calcium-evoked secretion from the adrenal medulla.

1. Experiments were carried out on cat adrenal glands perfused with Locke solution to study the effects of inhibition of metabolism on calcium-evoked catecholamine release.2. In the presence of sodium cyanide (CN, 0.2 mM), a low concentration of glucose (1 mM) prevented the gradual decline in the secretory response to sequential exposures to calcium. Furthermore, when the secretory response was almost completely blocked by perfusing with a glucose-deprived solution containing CN, restoration of secretion was correlated with the glucose concentration in the perfusion medium.3. In the presence of CN, 2-deoxyglucose blocked both the protective effect and the restorative effect of glucose. The deoxyglucose inhibition of the glucose-dependent restoration of secretion was antagonized by a higher concentration of glucose.4. Restoration of calcium-evoked secretion was also observed after the washout of CN. The extent of this restoration was not at all related to the glucose concentration and was not affected by various inhibitors of carbohydrate metabolism, including deoxyglucose.5. Analysis of adrenal glands which had been perfused first with a glucose-free solution containing CN and subsequently with the normal medium indicated that no discernible synthesis of catecholamines had taken place during the experimental procedures.6. The data provide further evidence that the action of calcium to trigger medullary secretion requires the presence of metabolic energy and support the hypothesis that an interaction between calcium and high-energy nucleotides is a step in the sequence of events leading to the extrusion of catecholamines from the chromaffin cell.