Analysis of opioid receptors and substance P activity in signal transduction and inflammation

我们发现了一种调节脑啡肽降解活性的内源性因子，并根据其对脑啡肽降解酶的抑制活性从牛脊髓中纯化了它。结构分析表明该因子为Leu-Val-Tyr-Pro-Trp-Thr，命名为spinorphin。研究发现，Spinorphin对猴脑中多种脑啡肽降解酶，尤其是二肽基肽酶III的活性有抑制作用。最近我们发现这种抑制剂能显著抑制缓激肽诱导的伤害性屈肌反应。我们还报道了spinorphin在炎症中的作用。Spinorphin可通过抑制中性粒细胞表面fMLF受体与中性粒细胞的结合而显著抑制中性粒细胞的功能。G蛋白偶联受体激酶（GRKs）磷酸化激动剂占据的G蛋白偶联受体，导致受体脱敏。我们研究了人类P物质受体是否是GRK 5的底物。我们报告，人P物质受体被磷酸化的纯化GRK 5。磷酸化具有高化学计量和低Km。这些结果首次证明了人P物质受体是GRK 5的底物。虽然Ach在学习记忆过程中的重要性已被指出在皮层和皮层中。本研究的目的是用纹状体胆碱能中间神经元来回答这个问题，并阐明其突触可塑性的机制。这里获得的结果表明如下。电刺激皮层/丘脑-纹状体通路可在胆碱能中间神经元上诱发去极化和超极化突触后电位，分别由皮层/丘脑-纹状体突触后电位（EPSP）和纹状体内诱发的双突触GABA能IPSP组成。

We found an endogenous factor that modulated enkephalin-degrating activity and purified it from bovine spinal cord based on its inhibitory activity toward enkephalin-degrading enzymes. Structural analysis revealed the factor to be Leu-Val-Tyr-Pro-Trp-Thr and it was named spinorphin. It has been found that spinorphin inhibited the activity toward various enkephalin-degrating enzymes from monkey brain, especially dipeptidyl peptidase III. Recently we found that this inhibitory significantly inhibited bradykin-induced nociceptive flexor responses. We also have reported roles for spinorphin in inflammation. Spinorphin significantly inhibited the functions of polymorphonuclear neutrophils by suppressing the binding of fMLF to its receptor on PMNs. The possible role of spinorphin as reglulators in pain and inflammation will be discussed.G protein coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors, leading to receptor desensitization. We investigated whether human substance P receptor is a substrate of GRK5. We report that human Substance P receptor is phosphorylated by purified GRK5. The phosphorylation has a high stoichiometry and a low Km. These data provide the first evidence that human substance P receptor is a substrate of GRK5.Although the importance of Ach in the learning and memory processes has been point out in the stratum as well as the cerebral cortex. The aim of our study was to answer this question using the striatal cholinergic inter-neurons and to elucidate the mechanism of synaptic plasticity in them. The results obtained here indicate the following. Electrical stimulation of cortico/thalamostriatal pathway frequently evokes a depolarizing and hyperpolarizing postsynaptic potential in the cholinergic inter-neurons that is composed of a cortic/thalamostriatal glutamatergic EPSP and an intrastriatally evoked disynaptic GABAergic IPSP, respectively.