γ-Preprotachykinin-(72-92)-Peptide Amide: An Endogenous Preprotachykinin I Gene-Derived Peptide that Preferentially Binds to Neurokinin-2 Receptors

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-01, Vol.87 (1), p.246-250
• Main Authors: Dam, Than-Vinh, Takeda, Yasuo, Krause, James E., Escher, Emanuel, Quirion, Rémi
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; ANIMALS; AUTORADIOGRAPHY; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; Binding sites; Binding, Competitive; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; BODY; BRAIN; Brain - metabolism; CELL CONSTITUENTS; Cell Membrane - metabolism; CELL MEMBRANES; CENTRAL NERVOUS SYSTEM; Dams; DAYS LIVING RADIOISOTOPES; ELECTRON CAPTURE RADIOISOTOPES; Fundamental and applied biological sciences. Psychology; Hippocampus; INTERMEDIATE MASS NUCLEI; IODINE 125; IODINE ISOTOPES; Iodine Radioisotopes; ISOTOPES; KINETICS; KININS; LIGANDS; Male; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; Messenger RNA; NERVOUS SYSTEM; Neuroscience; NUCLEI; ODD-EVEN NUCLEI; Organ Specificity; ORGANIC COMPOUNDS; ORGANS; Peptide Fragments - chemical synthesis; Peptide Fragments - metabolism; PEPTIDES; POLYPEPTIDES; PROTEINS; RADIOISOTOPES; Radioligand Assay; RATS; Rats, Inbred Strains; REACTION KINETICS; RECEPTORS; Receptors, Neurokinin-2; Receptors, Neurotransmitter - metabolism; RODENTS; SPECIFICITY; Substance P - metabolism; Tachykinins; Tachykinins - chemical synthesis; Tachykinins - metabolism; Thalamus; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• 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, γ-preprotachykinin-(72-92)-peptide amide [γ-PPT-(72-92)-NH2], a peptide derived by posttranslational processing of γ-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 γ-PPT-(72-92)-NH2are potent competitors of125I-labeled γ-PPT-(72-92)-NH2binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of125I-labeled γ-PPT-(72-92)-NH2and125I-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) and125I-labeled Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that γ-PPT-(72-92)-NH2binds to neurokinin-2 receptors and should be considered as a putative endogeneous ligand for this receptor class.