MECHANISM OF HISTAMINE-RELEASE INHIBITION BY NICOTINAMIDE IN IN VITRO ANTIGEN-ANTIBODY REACTION

Abstract

1. Nicotinamide inhibits histamine release by antigen from chopped lung tissue of a sensitized guinea pig. Addition of succinate potentiates this histamine release and accompanying increase in oxygen uptake. However, nicotinamide, though it inhibits increased release of histamine, does not inhibit the increased uptake of oxygen.2. Histamine release from guinea pig lung by sinomenine, compound 48/80, and decylamine, whose action is not considered to involve enzymatic process, differing from that of antigen, is also inhibited by nicotinamide.3. Nicotinamide inhibits anaphylactic contraction of guinea pig ileum and, apparently weakens passive cutaneous anaphylaxis.4. Inhibition of anaphylactic histamine release and contraction of plain muscle by nicotinamide does not prevent desensitization. The plain muscle, from which nicotinamide had been washed off, is capable of undergoing contraction in response to the antigen. Consequently, nicotinamide does not inhibit the union of antigen and antibody.5. Nicotinamide analogs which are DPNase inhibitor, such as nicotinic acid, isonicotinic acid hydrazide, pyridine-3-sulfonic acid, and iproniazid, also inhibit histamine release by antigen in various degrees.6. There is no difference in DPNase activity between sensitized and unsensitized guinea pig lungs. Antigen does not cause any observable change in the DPNase activity of sensitized guinea pig lung. Partially purified bovine spleen DPNase does not increase the release of histamine in vitro, either from the chopped lung tissue of a guinea pig or from subcellular large granules of a dog liver.7. The result, of present series of experiments suggests that the inhibition of histamine release by nicotinamide in antigen-antibody reaction is not the result of inhibition of DPNase but rather is of a type that blocks linking of chemical stimulation, caused by antigen-antibody union, with allergic changes proceeding inside the cell, by a mechanism different from that of respiratory enzyme inhibitors.