EFFECTS OF CYCLIC AMP-PHOSPHODIESTERASE AND CYCLIC GMP-PHOSPHODIESTERASE INHIBITORS ON IMMUNOLOGICAL RELEASE OF HISTAMINE AND ON LUNG CONTRACTION
EFFECTS OF CYCLIC AMP-PHOSPHODIESTERASE AND CYCLIC GMP-PHOSPHODIESTERASE INHIBITORS ON IMMUNOLOGICAL RELEASE OF HISTAMINE AND ON LUNG CONTRACTION
复制标题
DOI：
10.1111/j.1476-5381.1981.tb08748.x
复制
发表时间：
1981-01-01
影响因子：
7.3
通讯作者：
RUCKSTUHL, M
中科院分区：
文献类型：
--
作者：
FROSSARD, N;LANDRY, Y;RUCKSTUHL, M
1 ZK 62711和M & B 22948分别选择性抑制大鼠肺环腺苷酸（cAMP）和环鸟苷酸（cGMP）磷酸二酯酶活性。茶碱和罂粟碱抑制这两种活动。2卡巴胆碱收缩的大鼠肺条被4-（3-环戊氧基-4-甲氧基苯基）-2-吡咯烷酮（ZK 26711，EC 25 = 7 × 10（-8）M）和2-O-丙氧基苯基-8-氮杂嘌呤-6-酮（M & B 22948，EC 25 = 5 × 10（-7）M）舒张，表明环AMP和环GMP都具有舒张性质。3 ZK 62711对抗原诱导的人嗜碱性粒细胞组胺释放有抑制作用（IC_（25）= 8 × 10 ~（-7）M），而M & B 22948无此作用。而M & B 22948则抑制肥大细胞的释放（IC_（25））为10（-6）M，而ZK 62711则无此作用。[4]这些数据表明，cAMP对嗜碱性粒细胞组胺释放的抑制作用，而cGMP主要与肥大细胞有关。提示环核苷酸磷酸二酯酶抑制剂的抗过敏作用主要与环鸟苷酸的增加有关。
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.