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

Journal of Pharmacological Sciences

Nobuyuki Yanagihara²  Susumu Ueno¹  Yumiko Toyohira²  Takashi Kawasaki³  Takeyoshi Sata³  Go Obara³  Hirohide Inagaki²  Keita Takahashi²  Takafumi Horishita³  Masato Tsutsui⁴ 

[1] Department of Occupational Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan;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;Department of Pharmacology, Graduate School of Medicine, University of The Ryukyus, Japan

关键词: adrenal medullary cell;    descending noradrenergic inhibitory system;    norepinephrine transporter;    pentazocine;    SK-N-SH cell;   

DOI  :  10.1254/jphs.12164FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(4)(±)-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 Vmax with little change in the apparent Km, 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 Bmax without changing the apparent Kd. 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.

【 授权许可】

Unknown