Pharmacological characterization of vanilloid receptor located in the brain

Brain Res Mol Brain Res. 2002 Jan 31;98(1-2):51-7. doi: 10.1016/s0169-328x(01)00313-8.


Specific [3H]resiniferatoxin (RTX) binding detects the vanilloid receptor type I (VR1). In the present study we demonstrate specific, high-affinity, saturable [3H]RTX binding in various areas of monkey brain not known to be innervated by primary afferent neurons as well as in spinal cord and dorsal root ganglion neurons of the same origin. Detailed pharmacological characterization and comparison revealed no major difference in binding affinities between the peripheral and the central sites as measured by K(d)/K(i) values. In general, lower receptor density was measured in selected brain areas than in the periphery. Areas with higher receptor density were detected in the locus ceruleus, preoptic area, and medial basal hypothalamus of the brain. Both capsaicin and the competitive antagonist capsazepine inhibited the specific binding of [3H]RTX to membrane preparations of the dorsal horn of the spinal cord and dorsal root ganglia with K(i) values of 4.3+/-0.32 microM and 2.7+/-0.33 microM, respectively. Inhibition was observed in the central areas (hypothalamus) with K(i) values of 0.95+/-0.1 microM for capsaicin and 0.86+/-0.11 microM for capsazepine. Previous biological and pharmacological evidence suggested that vanilloid receptors were present in the brain. Our results demonstrate that the pharmacological properties of both the peripheral and central receptor sites display appropriate pharmacological similarity to represent the same receptor class. The modest differences in ligand affinities for the vanilloid receptor expressed in the brain nuclei and the dorsal root ganglion neurons may correspond to differences in sequence, modification or associated proteins.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain Chemistry* / drug effects
  • Capsaicin / analogs & derivatives*
  • Capsaicin / metabolism
  • Capsaicin / pharmacology
  • Diterpenes / metabolism
  • Diterpenes / pharmacology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Kinetics
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism
  • Macaca fascicularis
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Organ Specificity
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism
  • Receptors, Drug / drug effects*
  • Receptors, Drug / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Structure-Activity Relationship
  • TRPV Cation Channels


  • Diterpenes
  • Receptors, Drug
  • TRPV Cation Channels
  • TRPV1 receptor
  • resiniferatoxin
  • capsazepine
  • Capsaicin