Hall M E, Miley F, Stewart J M
Department of Biochemistry, University of Colorado Health Sciences Center, Denver 80262.
Peptides. 1989 Jul-Aug;10(4):895-901. doi: 10.1016/0196-9781(89)90132-0.
There is considerable evidence that substance P (SP) is a neurotransmitter in the CNS. Current findings suggest that the effects of synaptically released SP are terminated by enzymatic breakdown, primarily by endopeptidase 3.4.24.11 (endo 24.11). The products of cleavage by endo 24.11 include the amino-terminal fragment SP(1-7). Evidence suggests that SP is involved in mediating baroreceptor reflex activity in the nucleus of the solitary tract (NTS). Microinjection of SP into the NTS lowered blood pressure and heart rate. Microinjection of SP(1-7) into the NTS reproduced the effects of SP on both heart rate and blood pressure. Intra-NTS injection of phosphoramidon, an inhibitor of endo 24.11 activity, completely blocked the effects of a subsequent injection of SP. This blocking effect of phosphoramidon was unaltered by pretreatment with the opiate inhibitor naloxone. In contrast, phosphoramidon failed to block the depressor and bradycardic effects of SP(1-7). The implications of these findings regarding the role of endo 24.11 in the metabolism of SP are discussed.
有大量证据表明P物质（SP）是中枢神经系统中的一种神经递质。目前的研究结果表明，突触释放的SP的作用通过酶促降解而终止，主要是由内肽酶3.4.24.11（内肽酶24.11）进行降解。内肽酶24.11的裂解产物包括氨基末端片段SP(1-7)。有证据表明，SP参与介导孤束核（NTS）中的压力感受器反射活动。向NTS微量注射SP可降低血压和心率。向NTS微量注射SP(1-7)可重现SP对心率和血压的影响。向NTS内注射内肽酶24.11活性抑制剂磷酰胺素，可完全阻断随后注射SP的作用。磷酰胺素的这种阻断作用不会因用阿片类抑制剂纳洛酮预处理而改变。相比之下，磷酰胺素未能阻断SP(1-7)的降压和降心率作用。本文讨论了这些发现对于内肽酶24.11在SP代谢中的作用的意义。
