放线菌素D是NK2速激肽受体的竞争性和选择性拮抗剂。

Actinomycin D is a competitive and selective antagonist at NK2 tachykinin receptors.

作者信息

Patacchini R, Astolfi M, Brown M C, Maggi C A

机构信息

Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.

出版信息

Neuropeptides. 1991 Oct;20(2):109-14. doi: 10.1016/0143-4179(91)90060-v.

DOI:10.1016/0143-4179(91)90060-v

PMID:1665895

Abstract

The ability of actinomycin D, a known antineoplastic agent, to affect NK1 NK2 and NK3 tachykinin (TK) receptor types was assessed on several in vitro bioassays. Actinomycin D was completely ineffective as a TK antagonist in the guinea-pig ileum longitudinal muscle (GPI) and on the rat portal vein (RPV) (two issues containing NK1, and NK3 TK receptors, respectively) while it was a weak competitive antagonist in the endothelium-denuded rabbit pulmonary artery (RPA) and in the hamster trachea (HT) (tissues containing the NK2A and NK2B receptor subtypes, respectively). Furthermore actinomycin D was able to displace [125I]-His-NKA from NK2 receptor sites of the rat small intestine smooth muscle membranes. Although actinomycin D is about 3 orders of magnitude weaker as an NK2 antagonist as compared to the most effective ligands available, it could represent a starting point in the development of non-peptidic NK2 receptor antagonists.

摘要

在几种体外生物测定中评估了已知抗肿瘤药物放线菌素D对NK1、NK2和NK3速激肽（TK）受体类型的影响。放线菌素D在豚鼠回肠纵肌（GPI）和大鼠门静脉（RPV）（分别含有NK1和NK3 TK受体的两种组织）中作为TK拮抗剂完全无效，而在去内皮兔肺动脉（RPA）和仓鼠气管（HT）（分别含有NK2A和NK2B受体亚型的组织）中是一种弱竞争性拮抗剂。此外，放线菌素D能够从大鼠小肠平滑肌膜的NK2受体位点置换[125I]-组氨酸-NKA。尽管与现有的最有效配体相比，放线菌素D作为NK2拮抗剂的效力弱约3个数量级，但它可能是开发非肽类NK2受体拮抗剂的一个起点。