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Cloning and pharmacological characterization of mouse TRPV1.
Neurosci Lett. 2004 Nov 03; 370(1):55-60.NL

Abstract

The Transient Receptor Potential cation channel V1 (TRPV1) is expressed in peripheral nociceptive neurons and is subject to polymodal activation via various agents including capsaicin, noxious heat, low extracellular pH, and direct phosphorylation by protein kinase C (PKC). We have cloned and heterologously expressed mouse TRPV1 (mTRPV1) and characterized its function utilizing FLIPR-based calcium imaging to measure functional responses to various small molecule agonists, low pH and direct phosphorylation via PKC. The various TRPV1 agonists activated mTRPV1 with a rank order of agonist potency of (resiniferatoxin (RTX) = arvanil > capsaicin = olvanil > OLDA > PPAHV) (EC50 values of 0.15+/-0.04 nM, 0.27+/-0.07 nM, 9.1+/-1.2 nM, 3.7+/-0.3 nM, 258+/-105 nM, and 667+/-151 nM, respectively). Additionally, mTRPV1 was activated by either low pH or with addition of the PKC activator phorbol 12-myristate 13-acetate (PMA). The TRPV1 antagonists iodinated-resiniferatoxin (I-RTX) or BCTC were both able to block capsaicin, pH and PKC-induced responses of mTRPV1 (IC50 (I-RTX) = 0.35+/-0.12 nM, 1.9+/-0.7 nM, and 0.80+/-0.68 nM, IC50 (BCTC) = 1.3+/-0.36 nM, 0.59+/-0.16 nM, and 0.37+/-0.15 nM, respectively). However, the antagonist capsazepine was only able to inhibit a capsaicin-evoked response of mTRPV1 with an IC50 of 1426+/-316 nM. Comparable results were achieved with rat TRPV1, while capsazepine blocked all modes of human TRPV1 activation. Thus, the mTRPV1 cation channel has a molecular pharmacological profile more akin to rat TRPV1 than either human or guinea pig TRPV1 and the molecular pharmacology suggests that capsazepine may be an ineffective TRPV1 antagonist for in vivo models of inflammatory pain in the mouse.

Authors+Show Affiliations

Department of Neurobiology, Schering-Plough Research Institute, 2015 Galloping Hill Road, K15-1-1600 Kenilworth, NJ 07033, USA. craig.correll@spcorp.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15489017

Citation

Correll, Craig C., et al. "Cloning and Pharmacological Characterization of Mouse TRPV1." Neuroscience Letters, vol. 370, no. 1, 2004, pp. 55-60.
Correll CC, Phelps PT, Anthes JC, et al. Cloning and pharmacological characterization of mouse TRPV1. Neurosci Lett. 2004;370(1):55-60.
Correll, C. C., Phelps, P. T., Anthes, J. C., Umland, S., & Greenfeder, S. (2004). Cloning and pharmacological characterization of mouse TRPV1. Neuroscience Letters, 370(1), 55-60.
Correll CC, et al. Cloning and Pharmacological Characterization of Mouse TRPV1. Neurosci Lett. 2004 Nov 3;370(1):55-60. PubMed PMID: 15489017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cloning and pharmacological characterization of mouse TRPV1. AU - Correll,Craig C, AU - Phelps,P Tara, AU - Anthes,John C, AU - Umland,Shelby, AU - Greenfeder,Scott, PY - 2004/06/22/received PY - 2004/07/27/revised PY - 2004/07/28/accepted PY - 2004/10/19/pubmed PY - 2005/2/3/medline PY - 2004/10/19/entrez SP - 55 EP - 60 JF - Neuroscience letters JO - Neurosci. Lett. VL - 370 IS - 1 N2 - The Transient Receptor Potential cation channel V1 (TRPV1) is expressed in peripheral nociceptive neurons and is subject to polymodal activation via various agents including capsaicin, noxious heat, low extracellular pH, and direct phosphorylation by protein kinase C (PKC). We have cloned and heterologously expressed mouse TRPV1 (mTRPV1) and characterized its function utilizing FLIPR-based calcium imaging to measure functional responses to various small molecule agonists, low pH and direct phosphorylation via PKC. The various TRPV1 agonists activated mTRPV1 with a rank order of agonist potency of (resiniferatoxin (RTX) = arvanil > capsaicin = olvanil > OLDA > PPAHV) (EC50 values of 0.15+/-0.04 nM, 0.27+/-0.07 nM, 9.1+/-1.2 nM, 3.7+/-0.3 nM, 258+/-105 nM, and 667+/-151 nM, respectively). Additionally, mTRPV1 was activated by either low pH or with addition of the PKC activator phorbol 12-myristate 13-acetate (PMA). The TRPV1 antagonists iodinated-resiniferatoxin (I-RTX) or BCTC were both able to block capsaicin, pH and PKC-induced responses of mTRPV1 (IC50 (I-RTX) = 0.35+/-0.12 nM, 1.9+/-0.7 nM, and 0.80+/-0.68 nM, IC50 (BCTC) = 1.3+/-0.36 nM, 0.59+/-0.16 nM, and 0.37+/-0.15 nM, respectively). However, the antagonist capsazepine was only able to inhibit a capsaicin-evoked response of mTRPV1 with an IC50 of 1426+/-316 nM. Comparable results were achieved with rat TRPV1, while capsazepine blocked all modes of human TRPV1 activation. Thus, the mTRPV1 cation channel has a molecular pharmacological profile more akin to rat TRPV1 than either human or guinea pig TRPV1 and the molecular pharmacology suggests that capsazepine may be an ineffective TRPV1 antagonist for in vivo models of inflammatory pain in the mouse. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/15489017/Cloning_and_pharmacological_characterization_of_mouse_TRPV1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(04)00941-3 DB - PRIME DP - Unbound Medicine ER -