GAMMA-PREPROTACHYKININ-(72-92)-PEPTIDE AMIDE - AN ENDOGENOUS PREPROTACHYKININ-I GENE-DERIVED PEPTIDE THAT PREFERENTIALLY BINDS TO NEUROKININ-2 RECEPTORS

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)-NH2 are potent competitors of 125I-labeled γ-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled γ-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) binding sites are differentially located in this tissue. Thus, it appears that γ-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class.