Calcium requirement for the inhibition by theophylline of histamine release from mast cells

When added to Ca²⁺-free Hanks' solution, Ca²⁺ (0.1-2.5 mM) had no significant effect on antigen-induced histamine release from rat mast cells, but Sr²⁺ (1.0-3.0 mM) dose-dependently increased the release. Ba²⁺ (1.0 and 2.0 mM) also enhanced the release. Ca²⁺ and Ba²⁺ inhibited compound 40/80-induced histamine release, in a dose-dependent manner. In ordinary Hanks' medium, theophylline and 3-isobutyl-1-methylxanthine (IBMX) dose-dependently inhibited the antigen-induced histamine release but these drugs were ineffective in Ca²⁺-free medium. Theophylline (1.0 mM) also inhibited compound 48/80-induced histamine release in the presence but not absence of Ca²⁺. There was an optimal Ca²⁺ concentration for the theophylline effect. Sr²⁺ but not Ba²⁺ could substitute for Ca²⁺ in supporting the theophylline effect. Theophylline (1.0 mM) and IBMX (1.0 mM) increased mast cell cyclic AMP levels both in the presence and absence of Ca²⁺. These results suggest that Ca²⁺ is required in the interaction of theophylline and specific sites on mast cells or in the mast cell response to theophylline which probably does not involve the cyclic AMP increase and is linked to the inhibition of histamine release.