Subcutaneous injection of endokinin C/D attenuates carrageenan-induced inflammation.
Endokinins, encoded by the human preprotachykinin C (PPT-C)/TAC4 gene, are peptides that consist of endokinin A (EKA), B (EKB), C (EKC) and D (EKD) and belong to the tachykinin family. Intrathecal injection of EKC/D (using the common carboxyl-terminal duodecapeptide in EKC and EKD) markedly attenuated the induction of thermal hyperalgesia and scratching behavior by intrathecal administration of substance P (SP), indicating that EKC/D has an antagonistic effect on the neurokinin 1 receptor (NK1R), SP-preferring receptor, at the spinal level; however, the pharmacological function of EKC/D at the periphery is not yet understood. Therefore, to clarify the effect of EKC/D on the peripheral tissue, the effect of subcutaneous injection of EKC/D on carrageenan-induced inflammation was examined. Subcutaneous injection of EKC/D attenuated an increase in paw volume following carrageenan-induced inflammation in a dose-dependent manner. Indeed, the increased paw volume was significantly decreased 40 min after treatment with 10(-4) M (10 nmol) and 10(-3) M (100 nmol) EKC/D (100 microl/rat). Similarly, injection of NK1R antagonists such as L-703,606 and Spantide I (10(-3) M) attenuated the increased paw volume following inflammation. Furthermore, the reduced withdrawal latency evoked by inflammation following subcutaneous injection of carrageenan was also dose-dependently attenuated by EKC/D administration. These results indicate that subcutaneous injection of EKC/D elicits an anti-inflammatory effect on carrageenan-induced inflammation.
Naono-Nakayama
Rumi
R
Division of Neurobiology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan. rumi.n@fc.miyazaki-u.ac.jp
Sunakawa
Natsuki
N
Ikeda
Tetsuya
T
Matsushima
Osamu
O
Nishimori
Toshikazu
T
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006614:Hindlimb; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D009443:Neuritis / Q000139:chemically induced / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D018373:Peripheral Nervous System Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D015320:Tachykinins / Q000008:administration & dosage / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D002351:Carrageenan; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018373:Peripheral Nervous System Agents; D011812:Quinuclidines; D013373:Substance P; D015320:Tachykinins; C076851:L 703606; C042867:spantide; C486037:TAC4 protein, human