Masuda K, Suzuki K, Ishida-Okawara A, Mizuno S, Hotta K, Miyadoh S, Hara O, Koyama M
Department of Antibiotics, National Institute of Health, Tokyo, Japan.
J Antibiot (Tokyo). 1991 May;44(5):533-40. doi: 10.7164/antibiotics.44.533.
In order to search for microbial modulators of the activity of neuropeptide, we established a screen based on substance P (SP)-induced myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). SP induced MPO release in a dose-dependent manner at concentrations ranging from 1 approximately 10 x 10(-4) M. In comparison at 1 x 10(-4) M, induction was also observed with SP derivatives but not with other neuropeptides such as neurokinin and enkephalin. Based on this, we searched for microbial inhibitors against SP-induced MPO release. An actinomycete metabolite designated HS3, which turned out to be identical with dioxapyrrolomycin or A1-R2081, and structurally related pyrrolomycins were found to inhibit SP-induced MPO release. In addition, these compounds inhibited the f-Met-Leu-Phe (FMLP)-induced MPO release from PMN. Pyrrolomycin derivatives with an N-methylated pyrrole ring showed, however, a selective inhibition of the SP-induced MPO release. This was in contrast to results with aseanostatin P5 which selectively inhibited FMLP-induced MPO release.
为了寻找神经肽活性的微生物调节剂，我们建立了一种基于P物质（SP）诱导人多形核白细胞（PMN）释放髓过氧化物酶（MPO）的筛选方法。SP在1约10×10⁻⁴ M的浓度范围内以剂量依赖方式诱导MPO释放。相比之下，在1×10⁻⁴ M时，SP衍生物也能诱导MPO释放，而其他神经肽如神经激肽和脑啡肽则不能。基于此，我们寻找针对SP诱导的MPO释放的微生物抑制剂。一种放线菌代谢产物HS3，结果证明与二氧杂吡咯霉素或A1-R2081相同，以及结构相关的吡咯霉素被发现可抑制SP诱导的MPO释放。此外，这些化合物还抑制了f-甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）诱导的PMN释放MPO。然而，具有N-甲基化吡咯环的吡咯霉素衍生物对SP诱导的MPO释放表现出选择性抑制。这与阿塞诺他汀P5的结果相反，阿塞诺他汀P5选择性抑制FMLP诱导的MPO释放。
