The distribution and regulation of vanilloid receptor VR1 and VR1 5′ splice variant RNA expression in rat

被引:134
作者
Sanchez, JF [1 ]
Krause, JE [1 ]
Cortright, DN [1 ]
机构
[1] Neurogen Corp, Dept Biochem & Mol Biol, Branford, CT 06405 USA
关键词
vanilloid receptor; gene expression; resiniferatoxin; inflammation;
D O I
10.1016/S0306-4522(01)00373-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The vanilloid (capsaicin) receptor, VR1, is expressed in dorsal root ganglion and mediates the sensory response to vanilloids and other noxious stimuli. There is evidence for VRI expression in CNS regions as well. but its function in these tissues is unknown. The identification of a rat VRI 5' splice variant and the rat stretch inhibitable channel, which are also expressed in dorsal root ganglia and CNS, raises the possibility that these and/or other VRI variants may regulate VRI activity, We have used a quantitative ribonuclease protection assay to characterize the central and peripheral expression of VRI and VRI variant RNA in the rat. The data confirm that VRI is widely expressed in CNS, with highest RNA levels round in cerebral cortex, hippocampus, and cerebellum. VRI RNA expression in dorsal root ganglia is approximately 28 times greater than in any other tissue sample studied. VR1 5' splice variant RNA is expressed at levels 12 times lower than VRI in dorsal root ganglia, but at similar levels to VRI in all other tissues examined. A VRI-related RNA expressed at high levels in kidney was detected, and was distinct from VRI or stretch inhibitable channel. Our results also show that peripheral inflammation does not change VRI RNA levels in rat dorsal root ganglia. Systemic resiniferatoxin administration, however, decreases VRI expression in dorsal root ganglia by 65-80%, an effect that persists for at least 2 months. This study demonstrates that VRI is expressed at high levels in dorsal root ganglia relative to other tissues and that VRI 5' splice variant is expressed at low levels in dorsal root ganglia compared to VR1. VRI gene expression in dorsal root ganglia is regulated in response to systemic resiniferatoxin but not peripheral inflammation. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:373 / 381
页数:9
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