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Titolo:
Characterization using FLIPR of rat vanilloid receptor (rVR1) pharmacology
Autore:
Jerman, JC; Brough, SJ; Prinjha, R; Harries, MH; Davis, JB; Smart, D;
Indirizzi:
SmithKline Beecham Pharmaceut, Neurosci Res, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AW ssex, England
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 4, volume: 130, anno: 2000,
pagine: 916 - 922
SICI:
0007-1188(200006)130:4<916:CUFORV>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
ROOT GANGLION NEURONS; CAPSAICIN RECEPTOR; SENSORY NEURONS; RUTHENIUM RED; SPINAL-CORD; PAIN; RESINIFERATOXIN; CAPSAZEPINE; BINDING; CHANNEL;
Keywords:
vanilloid; capsaicin; calcium; ligand-gated ion channel; FLIPR; nociception;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Smart, D SmithKline Beecham Pharmaceut, Neurosci Res, New Frontiers Sci Pk,3rd Ave,Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut New Frontiers Sci Pk,3rd Ave Harlow Essex England CM19 5AW
Citazione:
J.C. Jerman et al., "Characterization using FLIPR of rat vanilloid receptor (rVR1) pharmacology", BR J PHARM, 130(4), 2000, pp. 916-922

Abstract

1 The vanilloid receptor (VR1) is a ligand-gated ion channel, which plays an important role in nociceptive processing. Therefore, a pharmacological characterization of the recently cloned rat VR1 (rVR1) was undertaken.2 HEK293 cells stable expressing rVR1 (rVR1-HEK293) were loaded with Fluo-3AM and then incubated at 25 degrees C for 30 min with or without various antagonists or signal transduction modifying agents. Then intracellular calcium concentrations ([Ca2+](i)) were monitored using FLIPR, before and afterthe addition of various agonists.3 The rank order of potency of agonists (resiniferatoxin (RTX) > capsaicin> olvanil > PPAHV) was as expected, and all were full agonists. The potencies of capsaicin and olvanil, but not RTX or PPAHV. were enhanced at pH 6.4(pEC(50) values of 7.47+/-0.06, 7.16+/-0.06, 8.19+/-0.06 and 6.02+/-0.03 respectively at pH 7.4 vs 7.71+/-0.05, 7.58+/-0.14, 8.10+/-0.05 and 6.04+/-0.08 at pH 6.4).4 Capsazepine, isovelleral and ruthenium red ail inhibited the capsaicin (100 nM)-induced Ca2+ response in rVR1-HEK293 cells, with pK(B) values of 7.52+/-0.08, 6.92+/-0.11 and 8.09+/-0.12 respectively (n = 6 each). The response to RTX and olvanil were also inhibited by these compounds. None displayed any agonist-like activity.5 The removal of extracellular Ca2+ abolished. whilst inhibition of protein kinase C with chelerythrine chloride (10 mu M) partially (similar to 20%)inhibited, the capsaicin (10 mu M)-induced Ca2+ response. However. tetrodotoxin (3 mu M), nimodipine (10 mu M), omega-GVIA conotoxin (100 mu M), thapsigargin (1 mu M), U73122 (3 mu M) or H-89 (3 mu M) had no effect on the capsaicin (100 nM)induced response.6 In conclusion, the recombinant rVR1 stably expressed in HEK293 cells acts as a ligand-gated Ca2+ channel with the appropriate agonist and antagonist pharmacology, and therefore is a suitable model for studying the effects of drugs at this receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 13:06:03