The cloned capsaicin receptor integrates multiple pain-producing stimuli.
Capsaicin, the main pungent ingredient in "hot" chili peppers, elicits buming pain by activating specific (vanilloid) receptors on sensory nerve endings. The cloned vanilloid receptor (VR1) is a cation channel that is also activated by noxious heat. Here, analysis of heat-evoked single channel currents in excised membrane patches suggests that heat gates VR1 directly. We also show that protons decrease the temperature threshold for VR1 activation such that even moderately acidic conditions (pH < or = 5.9) activate VR1 at room temperature. VR1 can therefore be viewed as a molecular integrator of chemical and physical stimuli that elicit pain. Immunocytochemical analysis indicates that the receptor is located in a neurochemically heterogeneous population of small diameter primary afferent fibers. A role for VR1 in injury-induced hypersensitivity at the level of the sensory neuron is presented.
Tominaga
M
M
Department of Cellular and Molecular Pharmacology, W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco 94143, USA.
Caterina
M J
MJ
Malmberg
A B
AB
Rosen
T A
TA
Gilbert
H
H
Skinner
K
K
Raumann
B E
BE
Basbaum
A I
AI
Julius
D
D
D000344:Afferent Pathways / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002460:Cell Line; D003001:Cloning, Molecular; D005727:Ganglia, Spinal / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009412:Nerve Fibers / Q000502:physiology*; D020078:Neurogenic Inflammation / Q000503:physiopathology; D009475:Neurons, Afferent / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology / Q000648:ultrastructure; D017783:Superior Cervical Ganglion / Q000502:physiology; D014162:Transfection; D014982:Xenopus laevis
D010446:Peptide Fragments; D011955:Receptors, Drug; D011994:Recombinant Proteins; D002211:Capsaicin