Holland L N, Goldstein B D, Aronstam R S
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Brain Res. 1993 Jan 8;600(1):89-96. doi: 10.1016/0006-8993(93)90405-c.
The repeated administration of a high dose of substance P (SP) onto the spinal cord has been shown to attenuate behavioral responses to an intense heat (tail-flick) or noxious mechanical stimulus (paw pressure). Studies performed to investigate the action of spinal SP have suggested that changes in behavioral responses involve endogenous opiate or neurokinin systems. This study was performed to investigate whether the binding characteristics of SP receptors in the dorsal horn are altered following successive administration of SP. Two populations of [3H]-SP binding sites were distinguished on the basis of their binding affinity. Gpp(NH)p, a stable analogue of GTP, decreased the size and affinity of the high affinity binding component selectively labelled with [125I]-Bolton Hunter-SP. Repeated intrathecal administration of SP (15 micrograms) which reduced behaviors also reduced the number and affinity of high affinity binding sites. Thus, attenuated behaviors in response to repeated administration of SP are paralleled by an alteration of SP binding in the dorsal horn. The altered agonist affinity seen under desensitizing conditions raises the possibility that SP receptor desensitization involves an uncoupling of receptor-G protein complexes.
已表明向脊髓反复给予高剂量的P物质（SP）会减弱对强烈热刺激（甩尾）或有害机械刺激（爪部压力）的行为反应。为研究脊髓SP的作用而进行的研究表明，行为反应的变化涉及内源性阿片或神经激肽系统。进行本研究以调查连续给予SP后背角中SP受体的结合特性是否发生改变。根据[3H]-SP结合位点的结合亲和力区分出两类结合位点。Gpp(NH)p是一种稳定的GTP类似物，它选择性地降低了用[125I]-博尔顿·亨特-SP标记的高亲和力结合成分的大小和亲和力。反复鞘内注射可减少行为的SP（15微克）也降低了高亲和力结合位点的数量和亲和力。因此，反复给予SP后行为减弱与背角中SP结合的改变同时出现。在脱敏条件下观察到的激动剂亲和力改变增加了SP受体脱敏涉及受体-G蛋白复合物解偶联的可能性。
