Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells

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 b2 receptors,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 b2 receptors,and μ-opioid receptors in b16-bl6 melanoma cells were observed. conclusion these results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. © 2016 institute of pharmacology,polish academy of sciences