Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites.
The vanilloid receptor (VR1) protein functions both as a receptor for capsaicin and a transducer of noxious thermal stimuli. To determine the expression and targetting of this protein, we have generated antisera against both the amino and carboxy termini of VR1. Within the dorsal root and trigeminal ganglia of rats, VR1-immunoreactivity (VR1-ir) was restricted to small and medium sized neurons. VR1-ir was transported into both the central and peripheral processes of these primary afferent neurons, as evidenced by: (i) the presence of VR1-ir in nerve fibres and terminals in lamina I and lamina II of the superficial dorsal horn, and the association of VR1-ir with small diameter nerve fibres in the skin and cornea; (ii) the reduction of VR1-ir in the spinal cord after dorsal rhizotomy; and (iii) the accumulation of VR1-ir proximal to sciatic nerve ligation. At the ultrastructural level, VR1-ir was associated with plasma membranes of neuronal perikarya in dorsal root ganglia and nerve terminals in the dorsal horn. VR1-ir was also seen in nerve fibres and terminals in the spinal trigeminal nucleus and nucleus of the solitary tract. Within a large proportion of dorsal root ganglion neurons and the terminals of their axons, VR1-ir was colocalized with staining for the P2X3 purinoceptor, and with binding sites for the lectin IB4. Surprisingly, VR1-ir did not coexist substantially in nerve fibres and terminals that contain substance P and calcitonin gene-related peptide, suggesting complex mechanisms for the release of these neuropeptides in response to capsaicin application.
Guo
A
A
Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis, MN 55455, USA.
Vulchanova
L
L
Wang
J
J
Li
X
X
Elde
R
R
D000818:Animals; D000918:Antibody Specificity; D015153:Blotting, Western; D002478:Cells, Cultured; D002772:Cholera Toxin; D017931:DNA Primers; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D006735:Horseradish Peroxidase; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000737:chemistry / Q000502:physiology; D009475:Neurons, Afferent / Q000737:chemistry* / Q000166:cytology / Q000648:ultrastructure; D009619:Nociceptors / Q000502:physiology; D051381:Rats; D011955:Receptors, Drug / Q000032:analysis* / Q000235:genetics* / Q000276:immunology; D018048:Receptors, Purinergic P2 / Q000032:analysis* / Q000235:genetics* / Q000276:immunology; D058477:Receptors, Purinergic P2X3; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D013347:Subcellular Fractions / Q000737:chemistry; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection
D017931:DNA Primers; C546407:P2RX3 protein, human; D011955:Receptors, Drug; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C052635:cholera toxin, B subunit-horseradish peroxidase; D002772:Cholera Toxin; D006735:Horseradish Peroxidase