HUMAN LUNG-TISSUE AND ANAPHYLAXIS .1. ROLE OF CYCLIC-GMP AS A MODULATOR OF IMMUNOLOGICALLY INDUCED SECRETORY PROCESS

[摘要] A close relationship was found between increased concentrations of cyclic GMP in human lung tissue and the capacity for acetylcholine to enhance the immunologic secretion of histamine and SRS-A [slow reacting substance of anaphylaxis] Acetylcholine (10-7-10-11 M) produced parallel increases in cyclic GMP and the immunologic release of mediators; the muscarinic blocking agent atropine prevented both responses. The increase in cyclic GMP in human lung after acetylcholine stimulation was apparent within 30 s, peaked by 120 s, and abruptly returned to control levels thereafter. The ability of acetylcholine to enhance the antigen-stimulated secretion of mediators followed the same time-course. PGF2.alpha. [prostaglandin F2.alpha.] (3.3 .times. 10-4 M to 3.3 .times. 10-7 M) increased the cyclic GMP content of human lung tissue in a dose-related fashion. Pretreatment of Ig[immunoglobulin]E-sensitized lung tissue with acetylsalicylic acid (10 .mu.g/ml) had no effect on baseline cyclic nucleotide levels, the capacity for antigen to induce mediator release, or the increase in cyclic GMP and facilitation of the immunologic release of mediators produced by acetylcholine.