Pentazocine Inhibits Norepinephrine Transporter Function by Reducing its Surface Expression in Bovine Adrenal Medullary Cells

• Obara Go

  Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Japan

• Toyohira Yumiko

  Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan

• Inagaki Hirohide

  Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan

• Takahashi Keita

  Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan

• Horishita Takafumi

  Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Japan

• Kawasaki Takashi

  Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Japan

• Ueno Susumu

  Department of Occupational Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan

• Tsutsui Masato

  Department of Pharmacology, Graduate School of Medicine, University of The Ryukyus, Japan

• Sata Takeyoshi

  Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Japan

• Yanagihara Nobuyuki

  Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan

抄録

(±)-Pentazocine (PTZ), a non-narcotic analgesic, is used for the clinical management of moderate to severe pain. To study the effect of PTZ on the descending noradrenergic inhibitory system, in the present study we examined the effect of [³H]norepinephrine (NE) uptake by cultured bovine adrenal medullary cells and human neuroblastoma SK-N-SH cells. (−)-PTZ and (+)-PTZ inhibited [³H]NE uptake by adrenal medullary cells in a concentration-dependent (3 – 100 μM) manner. Eadie-Hofstee analysis of [³H]NE uptake showed that both PTZs caused a significant decrease in the V_max with little change in the apparent K_m, suggesting non-competitive inhibition. Nor-Binaltorphimine and BD-1047, κ-opioid and σ-receptor antagonists, respectively, did not affect the inhibition of [³H]NE uptake induced by (−)-PTZ and (+)-PTZ, respectively. PTZs suppressed specific [³H]nisoxetine binding to intact SK-N-SH cells, but not directly to the plasma membranes isolated from the bovine adrenal medulla. Scatchard analysis of [³H]nisoxetine binding to SK-N-SH cells revealed that PTZs reduced the B_max without changing the apparent K_d. Western blot analysis showed a decrease in biotinylated cell-surface NE transporter (NET) expression after the treatment with (−)-PTZ. These findings suggest that PTZ inhibits the NET function by reducing the amount of NET in the cell surface membranes through an opioid and σ-receptor–independent pathway.

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 121 (2), 138-147, 2013

  公益社団法人 日本薬理学会

キーワード

• adrenal medullary cell
• descending noradrenergic inhibitory system
• norepinephrine transporter
• pentazocine
• SK-N-SH cell

詳細情報

• CRID: 1390282680157707136
• NII論文ID: 10031156943
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.12164fp
• COI: 1:CAS:528:DC%2BC3sXjvVyju7c%3D
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 024275067
• PubMed: 23370666
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024275067
• Web Site: https://search.jamas.or.jp/link/ui/2013290648
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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