The expression of P2X3 purinoreceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor.
We have studied the distribution and regulation of the P2X3 receptor (a ligand-gated ion channel activated by ATP) in adult dorsal root ganglion (DRG) neurons using a polyclonal antibody. P2X3 receptor immunoreactivity was normally present in about 35% of L4/5 DRG neurons, virtually all small in diameter. In the dorsal horn, P2X3 receptor expression was restricted to the terminals of sensory neurons terminating in lamina IIinner. P2X3 receptors were expressed in approximately equal numbers of sensory neurons projecting to skin and viscera but in very few of those innervating skeletal muscle. P2X3 receptors were found mostly in sensory neurons that bind the lectin IB4. After sciatic nerve axotomy, P2X3 receptor expression dropped by more than 50% in L4/5 DRG. Glial cell line-derived neurotrophic factor (GDNF), delivered intrathecally, completely reversed axotomy-induced down-regulation of the P2X3 receptor. We conclude that P2X3 receptors are normally expressed in nociceptive primary sensory neurons, predominantly the nonpeptidergic nociceptors. P2X3 receptors are down-regulated following peripheral nerve injury and their expression can be regulated by GDNF.
Bradbury
E J
EJ
Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College, London, SE1 7EH, United Kingdom.
Burnstock
G
G
McMahon
S B
SB
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D019771:Axotomy; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology* / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058477:Receptors, Purinergic P2X3; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D015740:Calcitonin Gene-Related Peptide