Yohimbine inhibits firing activities of rat dorsal root ganglion neurons by blocking Na+ channels and vanilloid VR1 receptors

被引：24

作者：

Dessaint, J ^{[1
]}

Yu, WF ^{[1
]}

Krause, JE ^{[1
]}

Yue, L ^{[1
]}

机构：

[1] Neurogen Corp, Dept Electrophysiol, Branford, CT 06405 USA

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2004年 / 485卷 / 1-3期

关键词：

yohimbine; Na+ channel; vanilloid VR1 receptor; dorsal root ganglion; action potential; firing activity;

D O I：

10.1016/j.ejphar.2003.11.039

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Yohimbine, an indole alkaloid, is a natural alpha(2)-adrenoceptor antagonist and is frequently used to assess the mechanism of a drug's effect on alpha-adrenoceptors. Recently, several studies showed that yohimbine exhibited analgesic effects in in vivo animal models. However, the underlying mechanism is not known. We investigated the effects of yohimbine on Na+ channels and vanilioid VR1 receptors in dorsal root ganglion cells. We found that yohimbine inhibited tetrodotoxin-sensitive Na+ channels (Na(v)1.2), the tetrodotoxin-resistant Na+ channels, including both slow inactivating (Na(v)1.8) and persistent (Na(v)1.9) Na+ channels, and capsaicin-sensitive vanilloid VR1 receptors. Action potential firing activities of dorsal root ganglion neurons evoked by current injection or capsaicin were eliminated by yohimbine. The blocking effects of yohimbine on nociceptive-related ion channels and firing activities of dorsal root ganglion neurons may underlie the ionic mechanism of yohimbine's analgesic effects observed in in vivo studies. (C) 2003 Elsevier B.V All rights reserved.

引用

页码：11 / 20

页数：10

共 47 条

[1] The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways [J].

Akopian, AN ;

Souslova, V ;

England, S ;

Okuse, K ;

Ogata, N ;

Ure, J ;

Smith, A ;

Kerr, BJ ;

McMahon, SB ;

Boyce, S ;

Hill, R ;

Stanfa, LC ;

Dickenson, AH ;

Wood, JN .

NATURE NEUROSCIENCE, 1999, 2 (06) :541-548

[2] A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons [J].

Akopian, AN ;

Sivilotti, L ;

Wood, JN .

NATURE, 1996, 379 (6562) :257-262

[3] Involvement of Na+ channels in pain pathways [J].

Baker, MD ;

Wood, JN .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2001, 22 (01) :27-31

[4] Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons [J].

Benn, SC ;

Costigan, M ;

Tate, S ;

Fitzgerald, M ;

Woolf, CJ .

JOURNAL OF NEUROSCIENCE, 2001, 21 (16) :6077-6085

[5] The vanilloid receptor: A molecular gateway to the pain pathway [J].

Caterina, MJ ;

Julius, D .

ANNUAL REVIEW OF NEUROSCIENCE, 2001, 24 :487-517

[6] Impaired nociception and pain sensation in mice lacking the capsaicin receptor [J].

Caterina, MJ ;

Leffler, A ;

Malmberg, AB ;

Martin, WJ ;

Trafton, J ;

Petersen-Zeitz, KR ;

Koltzenburg, M ;

Basbaum, AI ;

Julius, D .

SCIENCE, 2000, 288 (5464) :306-313

[7] The capsaicin receptor: a heat-activated ion channel in the pain pathway [J].

Caterina, MJ ;

Schumacher, MA ;

Tominaga, M ;

Rosen, TA ;

Levine, JD ;

Julius, D .

NATURE, 1997, 389 (6653) :816-824

[8] Sense and specificity: a molecular identity far nociceptors [J].

Caterina, MJ ;

Julius, D .

CURRENT OPINION IN NEUROBIOLOGY, 1999, 9 (05) :525-530

[9]

Cummins TR, 1997, J NEUROSCI, V17, P3503

[10] Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia [J].

Davis, JB ;

Gray, J ;

Gunthorpe, MJ ;

Hatcher, JP ;

Davey, PT ;

Overend, P ;

Harries, MH ;

Latcham, J ;

Clapham, C ;

Atkinson, K ;

Hughes, SA ;

Rance, K ;

Grau, E ;

Harper, AJ ;

Pugh, PL ;

Rogers, DC ;

Bingham, S ;

Randall, A ;

Sheardown, SA .

NATURE, 2000, 405 (6783) :183-187

← 1 2 3 4 5 →