What - if any - is the role of adrenergic mechanisms in histamine release from mast cells?

Abstract

The effects of catecholamines on histamine release from rat peritoneal mast cells, was studied in an in vitro system. It was found that norepinephrine (10(-5)-101(-3) M) exerts a significant, dose related, repressive effect on compound 48/80-induced histamine release. This effect is greatly potentiated by beta-antagonists and is noticeable throughout the concentration range 10(-11)-10(-3) M norepinephrine. Phentolamine diminishes the repressive effect that norepinephrine shows at 10(-5) M. Norepinephrine (10(-5) M) totally inhibits the progressive histamine release induced by both compound 48/80 and strontium (10 muM) in non-Ca2+-depleted cells. The release that is dependent on extracellular calcium is inhibited by norepinephrine. The repressive effect of norepinephrine at 10(-3) is counteracted by 5.6 mM D-glucose, 2-deoxyglucose abolishes this effect. The repression of histamine release by 10(-5) M norepinephrine is not influenced by D-glucose. These results suggest that the effects on histamine release, observed within a low concentration range of norepinephrine (less than 10(-3) M), may be due to alpha-adrenoreceptor mechanisms and an interference in transmembrane calcium transport. Our data further suggest that norepinephrine at 10(-3) M may inhibit oxidative phosphorylation. Isoproterenol and epinephrine (10(-9)-10(-5) M) show little effect on 48/80-induced histamine release in a normal medium. However, when calcium is excluded from the medium, histamine release is potentiated. These results seem to indicate that isoproterenol and epinephrine act by displacing intracellular calcium, making it available for the exocytosis process.