The common carboxyl-terminal region of novel tachykinin peptides contributes to induce desensitization in scratching behavior of rats

Some novel tachykinin peptides exhibiting homology with known members of the tachykinin family have been recently reported; however, little is known about the function of these peptides. Repeated intrathecal administration of substance P (SP) causes desensitization by binding SP to neurokinin 1 (NK1) receptor. Thus, to clarify the characteristics of the receptors involved in these novel peptides, we investigated whether desensitization is induced by intrathecal administration of these peptides in rats since desensitization is induced by binding these peptides to the receptor. Intrathecal administration of 10−3 M hemokinin-1 (HK-1) and 10−3 M decapeptide common in the carboxyl-terminal region of endokinin A and endokinin B (EKA/B) as well as SP evoked scratching behavior. When each peptide was administered twice with an interval of 15 min, remarkable desensitization of scratching behavior was produced. Furthermore, the first administration of EKA/B or SP produced clear cross-desensitization to SP, EKA/B and HK-1, whereas the first administration of HK-1 demonstrated weak cross-desensitization to EKA/B and SP. These results suggest that EKA/B and SP may bind to both the NK1 receptor and HK-1-preferred receptor, and HK-1 may preferentially bind to its preferred receptor.