Nyberg F, Le Grevés P, Terenius L
Department of Pharmacology, Uppsala, Sweden.
Biochimie. 1988 Jan;70(1):65-8. doi: 10.1016/0300-9084(88)90159-9.
Peptides with hormonal or neuronal activity are derived by enzymatic processing from pro-hormones, which by themselves are biologically inert. Processing and other enzymatic conversions may occur step-wise, leading to the formation of a cascade of biologically active (or inactive) peptides. The neurokin in substance P is known to be metabolically transformed both by amino- and endopeptidases. More N-terminal substance (1-7) has been found than C-terminal (2-11 to 5-11) fragments in various CNS areas. The substance P (1-7) fragment also shows biological activity e.g., providing analgesia, lowering blood pressure, inhibiting aggressive behavior and (in contrast to substance P) inhibiting grooming behavior. An endopeptidase generating substance P (1-7) and to a lesser extent, substance (1-8), has been isolated and characterized from human cerebrospinal fluid (CSF) and bovine spinal cord, as a metalloenzyme with essential SH-groups. Substance P co-exists with calcitonin gene related peptide (CGRP) in a large population of non-myelinated primary afferent ('pain') fibers. Intrathecal injection of substance P causes behavioral and physiological responses which are potentiated and prolonged by CGRP. It was found that CGRP competes with substance P for the endopeptidase. It is suggested that the main action of CGRP in the spinal cord is to inhibit substance P degradation.
具有激素或神经活性的肽是通过酶促加工从前体激素衍生而来的，前体激素本身是无生物活性的。加工和其他酶促转化可能逐步发生，导致形成一系列生物活性（或无活性）肽。已知P物质中的神经激肽可被氨基肽酶和内肽酶进行代谢转化。在各个中枢神经系统区域中，已发现更多的N端P物质（1-7）片段，而非C端（2-11至5-11）片段。P物质（1-7）片段也具有生物活性，例如提供镇痛作用、降低血压、抑制攻击行为以及（与P物质相反）抑制梳理行为。已从人脑脊液（CSF）和牛脊髓中分离并鉴定出一种产生P物质（1-7）且在较小程度上产生P物质（1-8）的内肽酶，它是一种具有必需巯基的金属酶。P物质与降钙素基因相关肽（CGRP）共存于大量无髓初级传入（“疼痛”）纤维中。鞘内注射P物质会引起行为和生理反应，而CGRP会增强并延长这些反应。研究发现，CGRP与P物质竞争内肽酶。有人提出，CGRP在脊髓中的主要作用是抑制P物质的降解。
