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Document Type |
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Article In Journal |
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Document Title |
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An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors |
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Document Language |
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English |
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Abstract |
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The vanilloid receptor VR1 is a nonselective cation channel that is
most abundant in peripheral sensory fibers but also is found in
several brain nuclei. VR1 is gated by protons, heat, and the pungent
ingredient of ‘‘hot’’ chili peppers, capsaicin. To date, no endogenous
compound with potency at this receptor comparable to that
of capsaicin has been identified. Here we examined the hypothesis,
based on previous structure-activity relationship studies and the
availability of biosynthetic precursors, that N-arachidonoyl-dopamine
(NADA) is an endogenous ‘‘capsaicin-like’’ substance in mammalian
nervous tissues. We found that NADA occurs in nervous
tissues, with the highest concentrations being found in the striatum,
hippocampus, and cerebellum and the lowest concentrations
in the dorsal root ganglion. We also gained evidence for the
existence of two possible routes for NADA biosynthesis and
mechanisms for its inactivation in rat brain. NADA activates both
human and rat VR1 overexpressed in human embryonic kidney
(HEK)293 cells, with potency (EC50 50 nM) and efficacy similar to
those of capsaicin. Furthermore, NADA potently activates native
vanilloid receptors in neurons from rat dorsal root ganglion and
hippocampus, thereby inducing the release of substance P and
calcitonin gene-related peptide (CGRP) from dorsal spinal cord
slices and enhancing hippocampal paired-pulse depression, respectively.
Intradermal NADA also induces VR1-mediated thermal hyperalgesia
(EC50 1.5 0.3 g). Our data demonstrate the
existence of a brain substance similar to capsaicin not only with
respect to its chemical structure but also to its potency at VR1
receptors |
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ISSN |
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0027-8424 |
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Journal Name |
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Proceedings of the National Academy of Sciences of the United States of America |
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Volume |
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99 |
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Issue Number |
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12 |
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Publishing Year |
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1423 AH
2002 AD |
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Article Type |
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Article |
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Added Date |
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Sunday, March 30, 2008 |
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Researchers
| عبدالمنعم الحياني | Al-Hayani, AbdulMonem | Researcher | Doctorate | |
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Files
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NADA paper, PNAS.pdf
| pdf | مشاهدة المقالة العلمية كاملة |
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