title: Pharmacological characteristics of endokinin C/D-derived peptides in nociceptive and inflammatory processing in rats.
abstract: Endokinins designated from the human TAC4 gene consist of endokinin A, endokinin B, endokinin C (EKC) and endokinin D (EKD). EKC/D is a peptide using the common carboxyl-terminal in EKC and EKD and consists of 12 amino acids, and exerts antagonistic effects on the induction of scratching behavior by substance P (SP). Some of SP-preferring receptor antagonists have several d-tryptophan (d-Trp); however, the pharmacological effect of EKC/D-derived peptides with d-Trp remains to be solved. Therefore, to clarify the pharmacological characteristics of EKC/D-derived peptides, effects of pretreatment with these peptides on SP-induced scratching and thermal hyperalgesia, formalin-induced flinching and carrageenan-induced inflammation were evaluated. Intrathecal administration of [d-Trp(8)]-EKC/D and [d-Trp(10)]-EKC/D showed a markedly long inhibitory effect, at least 14 h, whereas the antagonistic effects of [d-Trp(8,10)]-EKC/D and EKC/D without d-Trp disappeared after 1h. Furthermore, the inhibitory effect of [d-Trp(10)]-EKC/D-derived peptides was dependent on the number of amino acids from the amino-terminus, and the more numerous the amino acids, the more marked the antagonistic effect. Thus, these results indicate that the effective duration of EKC/D-derived peptides is dependent on the number of d-Trp in the carboxyl-terminal region and the amino-terminal region regulates the antagonistic effect of EKC/D.
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. rumi.n@fc.miyazaki-u.ac.jp
authors.forename: Rumi
authors.initials: R
authors.lastname: Naono-Nakayama
authors.forename: Natsuki
authors.initials: N
authors.lastname: Sunakawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsushima
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nishimori
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan / Q000009:adverse effects; D005557:Formaldehyde / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000628:therapy; D007279:Injections, Subcutaneous; D008297:Male; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000523:psychology; D010147:Pain Measurement / Q000379:methods; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000737:chemistry / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000009:adverse effects / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014364:Tryptophan / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D005557:Formaldehyde; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D013373:Substance P; D015320:Tachykinins; D014364:Tryptophan; C486037:TAC4 protein, human