Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate-related agents: II. Modification of histamine release by glycogenolytic metabolites

Abstract

d-glucose-6-phosphate (⩽ 5 × 10 −3 M), pyruvate, lactate (⩽ 1 × 10 −2 M), and dibutyryl cyclic AMP (⩽ 5 × 10 −3 M) were capable of inhibiting anaphylactic histamine release in vitro from chopped guinea pig lung. In lower concentrations, pyruvic acid and lactate, as well as dibutyryl cyclic AMP, enhanced the release. Significant synergism was observed between pyruvate (5 × 10 −3 M) and isoproterenol (1 × 10 −8 M) in the inhibition of histamine release. The inhibitory actions of isoproterenol, glucose-6-phosphate, and pyruvate were influenced by calcium ion concentration. However, beta blockade, which diminished the isoproterenol effect, was without effect on pyruvate (1 × 10 −2 M) or glucose-6-phosphate (5 × 10 −3 M) action. Reduction of histamine release as the result of blockade of glycolysis by 2-deoxy- d-glucose was slightly but reproducibly reversed by the addition of pyruvate (1 × 10 −2 M) to the release system. Glucose-6-phosphate and isoproterenol did not have this effect. The results, together with a previous study, suggest that glycogenolysis may possess a role in the anaphylactic histamine release in vitro from sensitized lung fragments.