New tachykinin peptides and nociception

Summary nin-1 (HK-1) and endokinins are peptides predicted from a new mammalian tachykinin gene, TAC4. The amino acid sequences derived from rat/mouse HK-1 and human HK-1 are not identical; however, the effects induced by intracerebroventricular or intrathecal administration of HK-1 are attenuated by treatment with antagonists of neurokinin 1 (NK1) receptor, substance P (SP) receptor, indicating that HK-1 is an agonist of the NK1 receptor. On the other hand, a growing body of evidence indicates that pharmacological characteristics of HK-1 and SP are always not identical, suggesting that the HK-1-preferred receptor may be involved in the effects of HK-1. Endokinins are derived from human TAC4 and consist of four endokinins, endokinin A (EKA), endokinin B (EKB), endokinin C (EKC) and endokinin D (EKD). Effects induced by intrathecal administration of EKA/B (the common C-terminal decapeptide in EKA and EKB) and SP were very similar, while the effects of SP and EKA/B were inhibited by EKC/D (the common C-terminal duodecapeptide in EKC and EKD). This inhibitory effect of EKC/D was derived from leucine at the carboxyl-terminus. These findings suggest that HK-1 and EKA/B have an agonistic effect, while EKC/D has an antagonistic effect on the NK1 receptor in nociceptive processing.