title: Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.
abstract: We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Fujita
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D045744:Cell Line, Tumor; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000235:genetics / Q000502:physiology
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)