Dam T V, Takeda Y, Krause J E, Escher E, Quirion R
Douglas Hospital Research Centre, McGill University, Verdun, Canada.
Proc Natl Acad Sci U S A. 1990 Jan;87(1):246-50. doi: 10.1073/pnas.87.1.246.
The presence of N-terminally extended forms of neurokinin A has recently been reported in the mammalian brain. Among them, gamma-preprotachykinin-(72-92)-peptide amide [gamma-PPT-(72-92)-NH2], a peptide derived by posttranslational processing of gamma-preprotachykinin, is most prominent. We report here that this peptide most likely acts on neurokinin-2 receptor sites since neurokinin A (a putative neurokinin-2 agonist) and gamma-PPT-(72-92)-NH2 are potent competitors of 125I-labeled gamma-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain. On the other hand, 125I-labeled Bolton-Hunter-substance P (a neurokinin-1 ligand) and 125I-labeled Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that gamma-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class.
最近有报道称,哺乳动物大脑中存在N端延伸形式的神经激肽A。其中,γ-前速激肽原-(72 - 92)-肽酰胺[γ-PPT-(72 - 92)-NH2]最为突出,它是γ-前速激肽原经翻译后加工衍生而来的一种肽。我们在此报告,该肽很可能作用于神经激肽-2受体位点,因为神经激肽A(一种假定的神经激肽-2激动剂)和γ-PPT-(72 - 92)-NH2是125I标记的γ-PPT-(72 - 92)-NH2结合的有效竞争者,而选择性神经激肽-1和-3激动剂则不是。此外,125I标记的γ-PPT-(72 - 92)-NH2和125I标记的神经激肽A结合位点在大鼠脑中的分布非常相似。另一方面,125I标记的博尔顿-亨特物质P(一种神经激肽-1配体)和125I标记的博尔顿-亨特蛙皮素(一种神经激肽-3配体)结合位点在该组织中的定位不同。因此,γ-PPT-(72 - 92)-NH2似乎与神经激肽-2受体结合,应被视为该受体类别的一种假定内源性配体。