cyclic-gmp and tranilast

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on histamine release from human leukocytes and from human and monkey lung fragments were investigated. WP-833 showed no inhibition of antigen, anti-immunoglobulin E (IgE)- and calcium ionophore A23187-induced histamine release from leukocytes of atopic patients allergic to house dust mite. In addition, no influences of WP-833 on the levels of cyclic adenosine monophosphate and guanosine monophosphate in leukocytes from healthy subjects were observed. However, antigen- or anti-IgE-mediated histamine release from human and monkey lung fragments passively sensitized in vitro with human serum IgE sensitive to mite antigen was clearly inhibited by WP-833. Interestingly, prolonged pretreatment of lung fragments with WP-833 resulted in a decay in inhibition of anaphylactic histamine release. Spontaneous histamine release from human leukocytes and monkey lung fragments were not inhibited by WP-833.

Topics: Animals; Azoles; Cromolyn Sodium; Cyclic AMP; Cyclic GMP; Female; Histamine Release; Immunoglobulin E; Leukocytes; Lung; Macaca; Male; ortho-Aminobenzoates; Tetrazoles

The molecular basis for the inhibitory action of the antiatopic drug, N-(3',4'-dimethoxycinnamoyl)anthranilic acid (Tranilast), on the thrombin-induced release of a lysosomal enzyme, beta-N-acetylglucosaminidase, from washed rabbit platelets was investigated. Tranilast dose dependently increased cyclic AMP and cyclic GMP levels in thrombin-stimulated platelets, parallel with the inhibition of beta-N-acetylglucosaminidase release. There was no significant effect of Tranilast on adenylate or guanylate cyclase activity. Tranilast inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterases in a cell-free system. The data suggest that the inhibitory action of Tranilast on the release reaction in platelets was due at least in part to inhibition of cyclic nucleotide phosphodiesterases followed by an elevation of cyclic AMP and cyclic GMP levels.

Topics: Acetylglucosaminidase; Aminoquinolines; Animals; Blood Platelets; Calcium; Chelating Agents; Cyclic AMP; Cyclic GMP; Female; In Vitro Techniques; Male; ortho-Aminobenzoates; Protein Kinase C; Rabbits