The distribution and regulation of vanilloid receptor VR1 and VR1 5' splice variant RNA expression in rat.
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 VR1 expression in CNS regions as well, but its function in these tissues is unknown. The identification of a rat VR1 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 VR1 variants may regulate VR1 activity. We have used a quantitative ribonuclease protection assay to characterize the central and peripheral expression of VR1 and VR1 variant RNA in the rat. The data confirm that VR1 is widely expressed in CNS, with highest RNA levels found in cerebral cortex, hippocampus, and cerebellum. VR1 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 VR1 in dorsal root ganglia, but at similar levels to VR1 in all other tissues examined. A VR1-related RNA expressed at high levels in kidney was detected, and was distinct from VR1 or stretch inhibitable channel. Our results also show that peripheral inflammation does not change VR1 RNA levels in rat dorsal root ganglia. Systemic resiniferatoxin administration, however, decreases VR1 expression in dorsal root ganglia by 65-80%, an effect that persists for at least 2 months. This study demonstrates that VR1 is expressed at high levels in dorsal root ganglia relative to other tissues and that VR1 5' splice variant is expressed at low levels in dorsal root ganglia compared to VR1. VR1 gene expression in dorsal root ganglia is regulated in response to systemic resiniferatoxin but not peripheral inflammation.
Sanchez
J F
JF
Department of Biochemistry and Molecular Biology, Neurogen Corporation, 35 N.E. Industrial Road, Branford, CT 06405, USA.
Krause
J E
JE
Cortright
D N
DN
D000818:Animals; D004274:DNA, Recombinant; D005727:Ganglia, Spinal / Q000378:metabolism; D014644:Genetic Variation; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
D004274:DNA, Recombinant; D012333:RNA, Messenger; D011955:Receptors, Drug