One-way cross-desensitization between P2X purinoceptors and vanilloid receptors in adult rat dorsal root ganglion neurones
Capsaicin and ATP can activate ligand-gated cation channels in nociceptive rat dorsal root ganglion (DRG) neurones. We have studied cross-desensitization between these two agents in rat isolated DRG neurones using the whole-cell voltage-clamp technique. ATP (10 μM) activated an inward current in DR...
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Published in | The Journal of physiology Vol. 523; no. 3; pp. 685 - 696 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
The Physiological Society
15.03.2000
Blackwell Science Ltd Blackwell Science Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Capsaicin and ATP can activate ligand-gated cation channels in nociceptive rat dorsal root ganglion (DRG) neurones. We have
studied cross-desensitization between these two agents in rat isolated DRG neurones using the whole-cell voltage-clamp technique.
ATP (10 μM) activated an inward current in DRG neurones at a holding potential of â60 mV. ATP evoked âfastâ responses that
underwent rapid activation and desensitization, âslowâ responses that activated and desensitized more slowly, or responses
that displayed a mixture of these two characteristics. The time course of the response to ATP was not related obviously to
capsaicin sensitivity.
Prior application of capsaicin (0·5 μM) increased the proportion of cells displaying only fast responses to ATP (10 μM) suggesting
that cross-desensitization had occurred between capsaicin and the slow component of the ATP response. Prior desensitization
to ATP had no apparent effect on the inward current response to capsaicin (0·5 μM).
Cross-desensitization between capsaicin and ATP was Ca 2+ dependent.
Changing the membrane holding potential ( V h ) to +40 mV for a brief period before applying ATP at â60 mV had a similar effect to capsaicin, i.e. the proportion of cells
displaying only fast responses to ATP was increased significantly. This effect of depolarization was not Ca 2+ dependent.
The heterogenity of responses to ATP is probably due to co-expression of homomeric P2X 3 receptors and heteromeric receptors comprising P2X 3 subunits with other P2X subunits. We propose that the change in time course of the ATP response produced by prior desensitization
to capsaicin is due to selective cross-desensitization with the heteromeric P2X receptors. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1111/j.1469-7793.2000.t01-1-00685.x |