垂体腺苷酸环化酶激活多肽对豚鼠气管平滑肌的舒张作用。

Relaxant effect of pituitary adenylate cyclase-activating polypeptide on guinea-pig tracheal smooth muscle.

作者信息

Araki N, Takagi K

机构信息

Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.

出版信息

Eur J Pharmacol. 1992 May 27;216(1):113-7. doi: 10.1016/0014-2999(92)90217-r.

DOI:10.1016/0014-2999(92)90217-r

PMID:1326435

Abstract

We investigated the relaxant effect of the pituitary adenylate cyclase-activating polypeptide with 27 residues (PACAP27) and with 38 residues (PACAP38) on guinea-pig tracheal smooth muscle. Both forms of PACAP showed dose-dependent relaxant effects. The EC50 of PACAP27 was 8.7 +/- 1.9 x 10(-8) M and that of PACAP38 was 6.8 +/- 1.0 x 10(-8) M. Both increased cyclic AMP levels dose dependently and the elevation of cyclic AMP preceded the relaxation of tracheal smooth muscle. There was a marked difference in the duration of action of the two peptides. PACAP38 showed a longer-lasting relaxation compared to PACAP27. Furthermore PACAP38 maintained significantly higher levels of cyclic AMP, with cyclic AMP levels at 60 min after a 5-min exposure to PACAPs (10(-6) M) being 14.0 +/- 1.4 pM/mg protein for PACAP27 and 35.9 +/- 2.4 pM/mg protein for PACAP38. These results suggest that PACAP27 and PACAP38 may be novel potent relaxants in tracheal smooth muscle and their relaxant effect might be mediated by cyclic AMP. However PACAP38 had a longer-lasting action on relaxation of tracheal smooth muscle and production of tissue cyclic AMP than PACAP27.

摘要

我们研究了27个氨基酸残基的垂体腺苷酸环化酶激活多肽（PACAP27）和38个氨基酸残基的垂体腺苷酸环化酶激活多肽（PACAP38）对豚鼠气管平滑肌的舒张作用。两种形式的PACAP均呈现剂量依赖性舒张作用。PACAP27的半数有效浓度（EC50）为8.7±1.9×10⁻⁸ M，PACAP38的半数有效浓度为6.8±1.0×10⁻⁸ M。二者均能剂量依赖性地升高环磷酸腺苷（cAMP）水平，且cAMP水平升高先于气管平滑肌舒张。两种多肽的作用持续时间存在显著差异。与PACAP27相比，PACAP38的舒张作用持续时间更长。此外，PACAP38能使cAMP水平维持在显著更高的水平，在暴露于PACAPs（10⁻⁶ M）5分钟后60分钟时，PACAP27组的cAMP水平为14.0±1.4 pM/mg蛋白，PACAP38组为35.9±2.4 pM/mg蛋白。这些结果表明，PACAP27和PACAP38可能是气管平滑肌新型强效舒张剂，其舒张作用可能由cAMP介导。然而，与PACAP27相比，PACAP38对气管平滑肌舒张和组织cAMP生成的作用持续时间更长。