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A full pharmacological characterisation of the recently cloned human vanilloid VR1 receptor was undertaken. In whole-cell patch clamp studies, capsaicin (10 microM) elicited a slowly activating/deactivating inward current in human embryonic kidney (HEK293) cells stably expressing human vanilloid VR1 receptor, which exhibited pronounced outward rectification (reversal potential -2.1+/-0.2 mV) and was abolished by capsazepine (10 microM). In FLIPR-based Ca(2+) imaging studies the rank order of potency was resiniferatoxin>olvanil>capsaicin>anandamide, and all were full agonists. Isovelleral and scutigeral were inactive (1 nM-30 microM). The potencies of capsaicin, olvanil and resiniferatoxin, but not anandamide, were enhanced 2- to 7-fold at pH 6.4. Capsazepine, isovelleral and ruthenium red inhibited the capsaicin (100 nM)-induced Ca(2+) response (pK(B)=6.58+/-0.02, 5.33+/-0.03 and 7.64+/-0.03, respectively). In conclusion, the recombinant human vanilloid VR1 receptor stably expressed in HEK293 cells acted as a ligand-gated, Ca(2+)-permeable channel with similar agonist and antagonist pharmacology to rat vanilloid VR1 receptor, although there were some subtle differences.

Type

Journal article

Journal

Eur J Pharmacol

Publication Date

06/04/2001

Volume

417

Pages

51 - 58

Keywords

Alkaloids, Aniline Compounds, Arachidonic Acids, Benzophenanthridines, Calcium, Capsaicin, Cell Line, Diterpenes, Dose-Response Relationship, Drug, Endocannabinoids, Enzyme Inhibitors, Fluorescence, Fluorometry, Humans, Hydrogen-Ion Concentration, Membrane Potentials, Phenanthridines, Polyunsaturated Alkamides, Protein Kinase C, Receptors, Drug, Ruthenium Red, Sesquiterpenes, Time Factors, Xanthenes