CB1 receptor antagonist SR141716A increases capsaicin-evoked release of Substance P from the adult mouse spinal cord

被引:39
作者
Lever, IJ [1 ]
Malcangio, M [1 ]
机构
[1] Kings Coll London, Guys Kings & St Thomas Sch Biomed Sci, Neurosci Res Ctr, London SE1 1UL, England
关键词
cannabinoids; Substance P; spinal cord; sensory neurones;
D O I
10.1038/sj.bjp.0704506
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cannabinoids have an antinociceptive action in many pain models. We have investigated a possible modulatory role for Type 1 Cannabinoid receptors (CB1) on the release of excitatory transmitter Substance P from the adult mouse spinal cord after stimulation of nociceptor terminals by capsaicin. Capsaicin (0.1 - 10 muM) was applied to superfused cord sections and evoked a dose dependent release of SP above basal outflow of (23.36+/-2.96 fmol 8 ml(-1)). Maximum evoked SP release was obtained with 5 muM Capsaicin (262.4+/-20.8 fmol 8 ml(-1)). Higher capsaicin concentrations (50 - 100 mum) evoked less SP release. Superfusion of CB1 antagonist SR141716A (5 muM) increased evoked SP release with capsaicin (0.1-10 muM) and reversed the reducing effect of high dose capsaicin (100 km). Antagonism of CB1 receptors in the spinal cord during capsaicin stimulation, is evidence of tonic CB1 activity inhibiting the release of excitatory transmitters after activation of nociceptive neurones and is also indicative of endocannabinoid production during noxious stimulation.
引用
收藏
页码:21 / 24
页数:4
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