Energy metabolism in rat mast cells in relation to histamine secretion

Abstract

1. The relation between the energy metabolism and the secretory activity of rat peritoneal mast cells has been studied by determination of the cellular content of ATP and the rate of lactate production reflecting the rate of ATP synthesis under various experimental conditions. Secretion of histamine was induced by the antigen-antibody reaction, the polymeric amine compound 48/80, and the divalent ionophore A23187. 2. In presence of low concentrations of metabolic inhibitors (oligomycin or antimycin A) a linear relation between the secretion of histamine induced by all three liberators and the cellular ATP content at the time of cell activation was demonstrated. This may indicate a direct link between ATP and the secretory mechanism. 3. The possibility of an increased utilization of ATP during histamine secretion was explored in mast cells exposed to metabolic inhibitors. Incubation of mast cells with 2-deoxyglucose (2-DG) decreased the ATP content of the cells, and a long-lasting and stable level of mast cell ATP was observed. This is explained by a small decrease in the rate of ATP-synthesis by 2-DG. In 2-DG-treated cells secretion of histamine in response to compound 48/80 or the antigen-antibody reaction could still occur, and the secretion is shown to be associated with a decrease of the cellular ATP level. This ATP decrease indicates that secretion occurs by an ATP-requiring mechanism, that causes an increased cellular utilization of ATP in association with the secretory response. 4. The possibility has been considered that increased cytosol concentration of calcium in association with secretion may decrease the rate of ATP-synthesis due to accumulation of calcium by the mitochondria. This possibility can be excluded by the observation that in presence of respiratory inhibitors an identical ATP decrease was found during the secretion as in the case of the glycolytic inhibitor alone. This indicates that increased utilization of ATP by the cells was related directly to the secretory response. This observation was made with all three secretagogues. 5. A quantitative evaluation of the increased amount of ATP utilized by the cells in relation to the secretory response was performed by use of metabolic inhibitors. The ATP requirement of compound 48/80-induced secretion was 0.15 pmol/10(3) cells. This was observed when the ATP-synthesis was decreased to a negligible value.(ABSTRACT TRUNCATED AT 400 WORDS)