title: Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.
abstract: BACKGROUND
  Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells.
  
  
  METHODS
  The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B2receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry.
  
  
  RESULTS
  Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B2receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed.
  
  
  CONCLUSIONS
  These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. Electronic address: andoht@pha.u-toyama.ac.jp.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shinohara
authors.affiliation: Research Administration Division, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005283:Fentanyl / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D019332:Endothelin-1; D017450:Receptors, Opioid, mu; D001920:Bradykinin; D005283:Fentanyl
keywords: Bradykinin; Endothelin-1; Fentanyl citrate; Kinin B(2) receptors; μ-Opioid receptors