Low-threshold heat response antagonized by capsazepine in chick sensory neurons, which are capsaicin-insensitive.
The heat-transducing receptor VR1 cloned from rat sensory neurons can be activated by both noxious heat and capsaicin. As the response of sensory neurons to capsaicin is species dependent, it is conceivable that the responses to noxious heat and to capsaicin are transduced by distinct receptors across different species. Therefore, we investigated responses to noxious heat from a capsaicin-insensitive (chick) and a capsaicin-sensitive (rat) species. In chick, whole-cell patch-clamp experiments in isolated dorsal root ganglion neurons revealed two populations of neurons with different thresholds to noxious heat, activated at approximately 43 degrees C and approximately 53 degrees C. In cobalt uptake experiments, the proportion of neurons showing a heat-induced response increased with increasing heat stimuli. Application of capsaicin (1-10 microM) did not result in inward currents or cobalt uptake. Rat neurons yielded comparable results in heat experiments, but were capsaicin-sensitive. Although chick neurons are insensitive to capsaicin, the competitive capsaicin antagonist capsazepine (1-10 microM) was effective in blocking heat-induced responses, verified by patch-clamp and cobalt uptake methods. The noncompetitive capsaicin antagonist ruthenium red (10 microM) reduced to almost nil the proportion of heat-responsive neurons identified with the cobalt uptake method. These findings suggest that chick DRG neurons express a low-threshold heat-transducing receptor with a pharmacological profile distinct from the low-threshold heat receptor VR1 cloned from rat DRG neurons. The data support the idea that there might be heat receptor subtypes with differences in the capsaicin binding site.
Marín-Burgin
A
A
Department of Physiology, University of Würzburg, Röntgenring 9, D-97070 Würzburg, Germany.
Reppenhagen
S
S
Klusch
A
A
Wendland
J R
JR
Petersen
M
M
D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens / Q000033:anatomy & histology / Q000378:metabolism; D003035:Cobalt / Q000378:metabolism / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology; D013697:Thermosensing / Q000502:physiology*
D007473:Ion Channels; D012430:Ruthenium Red; D003035:Cobalt; C071423:capsazepine; D002211:Capsaicin