Effects of cyclic AMP- and cyclic GMP- phosphodiesterase inhibitors on immunological release of histamine and on lung contraction.

Abstract

1 Cyclic adenosine 3',5'-monophosphate (cyclic AMP)- and cyclic guanosine 3',5'-monophosphate (cyclic GMP)-phosphodiesterase activities from rat lung were selectively inhibited by ZK 62711 and M & B 22948, respectively. Theophylline and papaverine inhibited both activities. 2 Rat lung strips contracted by carbachol were relaxed by 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 26711, EC25 = 7 x 10(-8)M) and 2-O-propoxyphenyl-8-azapurin-6-one (M & B 22948, EC25 = 5 x 10(-7)M) indicating relaxant properties of both cyclic AMP and cyclic GMP. 3 The antigen-induced histamine release from human basophils was inhibited by ZK 62711 (IC25 = 8 x 10(-7)M), whereas M & B 22948 had no effect. On the contrary, the release from rat mast cells was inhibited by M & B 22948 (IC25 = 10(-6)M), while ZK 62711 had no effect. 4 These data show an inhibitory effect of cyclic AMP on histamine release to be involved with basophils, whereas cyclic GMP is predominantly involved with mast cells. Is is suggested that the antianaphylactic properties of cyclic nucleotide phosphodiesterase inhibitors are mainly linked to the increase of cyclic GMP.