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Pharmacol Rep. 2017 Feb;69(1):139-142. doi: 10.1016/j.pharep.2016.10.005. Epub 2016 Oct 6.

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

Author information

1
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.
2
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
3
Research Administration Division, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.

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 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.

KEYWORDS:

Bradykinin; Endothelin-1; Fentanyl citrate; Kinin B(2) receptors; μ-Opioid receptors

PMID:
27919002
DOI:
10.1016/j.pharep.2016.10.005
[Indexed for MEDLINE]

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