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TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons.
Neurosci Lett. 2008 Jun 20; 438(2):221-7.NL

Abstract

TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17 degrees C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised with a subset of hDRG neurons positive for TRPV1, the heat and capsaicin receptor. The number of small/medium TRPA1 positive neurons (< or =50 microm) was increased after hDRG avulsion injury [percentage of cells, median (range): controls 16.5 (7-23); injured 46 (34-55); P<0.005], but the number of large TRPA1 neurons was unchanged [control 19.5 (13-31); injured 21 (11-35)]. Similar TRPA1 changes were observed in cultured hDRG neurons, after exposure to a combination of key neurotrophic factors NGF, GDNF and NT-3 (NTFs) in vitro. We used calcium imaging to examine responses of HEK cells transfected with hTRPA1 cDNA, and of human and rat DRG neurons cultured with or without added NTFs, to cinnamaldehyde (CA) and isoeugenol (IE). Exposure to NTFs in vitro sensitized cultured human sensory neuronal responses to CA; repeated CA exposure produced desensitisation. In rDRG neurons, low (225 microM) CA preincubation enhanced capsaicin responses, while high (450 microM and 2mM) CA caused inhibition which was partially reversed in the presence of 8 bromo cAMP, indicating receptor dephosphorylation. While TRPA1 localisation is more widespread than TRPV1, it represents a promising novel drug target for the treatment of chronic pain and hypersensitivity.

Authors+Show Affiliations

Peripheral Neuropathy Unit, Imperial College London, Area A, Ground Floor, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. uma.anand@cancer.org.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18456404

Citation

Anand, U, et al. "TRPA1 Receptor Localisation in the Human Peripheral Nervous System and Functional Studies in Cultured Human and Rat Sensory Neurons." Neuroscience Letters, vol. 438, no. 2, 2008, pp. 221-7.
Anand U, Otto WR, Facer P, et al. TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons. Neurosci Lett. 2008;438(2):221-7.
Anand, U., Otto, W. R., Facer, P., Zebda, N., Selmer, I., Gunthorpe, M. J., Chessell, I. P., Sinisi, M., Birch, R., & Anand, P. (2008). TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons. Neuroscience Letters, 438(2), 221-7. https://doi.org/10.1016/j.neulet.2008.04.007
Anand U, et al. TRPA1 Receptor Localisation in the Human Peripheral Nervous System and Functional Studies in Cultured Human and Rat Sensory Neurons. Neurosci Lett. 2008 Jun 20;438(2):221-7. PubMed PMID: 18456404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons. AU - Anand,U, AU - Otto,W R, AU - Facer,P, AU - Zebda,N, AU - Selmer,I, AU - Gunthorpe,M J, AU - Chessell,I P, AU - Sinisi,M, AU - Birch,R, AU - Anand,P, Y1 - 2008/04/08/ PY - 2008/03/20/received PY - 2008/04/02/revised PY - 2008/04/02/accepted PY - 2008/5/6/pubmed PY - 2008/9/20/medline PY - 2008/5/6/entrez SP - 221 EP - 7 JF - Neuroscience letters JO - Neurosci Lett VL - 438 IS - 2 N2 - TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17 degrees C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised with a subset of hDRG neurons positive for TRPV1, the heat and capsaicin receptor. The number of small/medium TRPA1 positive neurons (< or =50 microm) was increased after hDRG avulsion injury [percentage of cells, median (range): controls 16.5 (7-23); injured 46 (34-55); P<0.005], but the number of large TRPA1 neurons was unchanged [control 19.5 (13-31); injured 21 (11-35)]. Similar TRPA1 changes were observed in cultured hDRG neurons, after exposure to a combination of key neurotrophic factors NGF, GDNF and NT-3 (NTFs) in vitro. We used calcium imaging to examine responses of HEK cells transfected with hTRPA1 cDNA, and of human and rat DRG neurons cultured with or without added NTFs, to cinnamaldehyde (CA) and isoeugenol (IE). Exposure to NTFs in vitro sensitized cultured human sensory neuronal responses to CA; repeated CA exposure produced desensitisation. In rDRG neurons, low (225 microM) CA preincubation enhanced capsaicin responses, while high (450 microM and 2mM) CA caused inhibition which was partially reversed in the presence of 8 bromo cAMP, indicating receptor dephosphorylation. While TRPA1 localisation is more widespread than TRPV1, it represents a promising novel drug target for the treatment of chronic pain and hypersensitivity. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/18456404/TRPA1_receptor_localisation_in_the_human_peripheral_nervous_system_and_functional_studies_in_cultured_human_and_rat_sensory_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(08)00467-9 DB - PRIME DP - Unbound Medicine ER -