Delay-Goyet P, Lundberg J M
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Biochem Biophys Res Commun. 1991 Nov 14;180(3):1342-9. doi: 10.1016/s0006-291x(05)81343-9.
Dactinomycin, a peptide antibiotic from Streptomyces spp., is a classical agent which inhibits DNA replication. In the present study, dactinomycin inhibited specific [125I]NKA binding in rat colon membranes (KI = 1.05 x 10(-5) M) in a competitive manner. Furthermore, dactinomycin caused a parallel rightward shift of the concentration-response curve for the contractions in the rat colon induced by the NK-2 receptor agonist [Nle10]-NKA(4-10). A selective inhibition of NK-2 receptors by dactinomycin was supported by the absence of inhibition of NK-1 receptors activation in guinea pig vas deferens and of NK-3 receptors in rat portal vein. The structural similarity of the cyclic peptide moieties of dactinomycin to L-659,877, a known NK-2 receptor antagonist, can probably account for the present observations.
放线菌素是一种来自链霉菌属的肽类抗生素，是一种抑制DNA复制的经典药物。在本研究中，放线菌素以竞争性方式抑制大鼠结肠膜中特异性[125I]NKA结合（KI = 1.05×10(-5) M）。此外，放线菌素使NK-2受体激动剂[Nle10]-NKA(4-10)诱导的大鼠结肠收缩的浓度-反应曲线平行右移。豚鼠输精管中NK-1受体激活未受抑制以及大鼠门静脉中NK-3受体未受抑制，支持了放线菌素对NK-2受体的选择性抑制作用。放线菌素的环肽部分与已知的NK-2受体拮抗剂L-659,877的结构相似性，可能是造成目前观察结果的原因。
