Planta Med 2012; 78(09): 874-880
DOI: 10.1055/s-0031-1298471
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Oxysophoridine through Intrathecal Injection Induces Antinociception and Increases the Expression of the GABAAα1 Receptor in the Spinal Cord of Mice

Guang Yang
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
,
Jinxian Gao
2   Department of Pharmacy, the Peopleʼs Hospital of Gansu Province, Gansu, China
,
Yuexia Jia
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
,
Lin Yan
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
,
Jianqiang Yu
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
,
Yuanxu Jiang
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
› Institutsangaben
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Publikationsverlauf

received 23. Dezember 2011
revised 21. März 2012

accepted 26. März 2012

Publikationsdatum:
24. April 2012 (online)

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Abstract

Our researches in recent years have shown that oxysophoridine (OSR), an alkaloid extracted from Siphocampylus verticillatus, presents antinociception through systemic and intracerebroventricular (icv) administration, and that OSR can also increase the GABA-immunopositive cells number in the central nervous system in rats. The purpose of the present study was to investigate the antinociception produced by OSR administered spinally, the interaction between OSR and GABAA receptor (GABAAR) agonists or antagonists on acute thermal nociceptive models (tail-flick test), and the possible alterations on the mRNA and protein expression of GABAAα1 receptors in the spinal cord. ICR mice were tested for their tail withdrawal response to thermal stimulation (tail-flick test). Quantitative real-time PCR and Western blot were used to inspect the influence of OSR administered by intrathecal injection (i. t.) on mRNA and protein expression of the GABAAα1 receptor in mice spinal cord by the formalin test. The experiments showed that OSR (0.13–0.25 mg/site, i. t.) significantly increased the tail withdrawal threshold with a peak effect of 68.35 % MPE at 20 min (p < 0.01). When OSR (0.06 mg/site, i. t.) was administered with gamma aminobutyric acid (GABA) (30.0 µg/site, icv) or muscimol (MUS) (0.10 µg/site, icv), the value of tail-flick latency was remarkably larger than with OSR alone (at 10 min, 45.67 % or 31.45 %, p < 0.01). Picrotoxin (PTX) and bicuculine (BIC) can significantly antagonize the antinociception of OSR. OSR (0.25 mg/site, i. t.) can increase the expression of mRNA and protein of the GABAAα1 receptor in the spinal cord (L5–L6). The results reveal that i. t. administered OSR presents effective antinociception whose action is mainly located in the spinal cord. The antinociception of OSR results from the activation of the GABAA receptor and from the regulation of the GABAAα1 receptor-mediated neurotransmission.