title: Modulation of human TRPV1 receptor activity by extracellular protons and host cell expression system.
abstract: The transient receptor potential vanilloid 1 (TRPV1) receptor is a ligand-gated cation channel that can be activated by capsaicin, heat, protons and cytosolic lipids. We compared activation of recombinant human TRPV1 receptors stably expressed in human 293 cells, derived from kidney embryonic cells, and in human 1321N1 cells, derived from brain astrocytes. Cellular influx of calcium was measured in response to acid, endovanilloids (N-arachidonoyl-dopamine, N-oleoyl-dopamine and anandamide), capsaicin and other traditional vanilloid agonists under normal (pH 7.4) and acidic (pH 6.7 and 6.0) assay conditions. The host cell expression system altered the agonist profile of endogenous TRPV1 receptor agonists without affecting the pharmacological profile of either exogenous TRPV1 receptor agonists or antagonists. Our data signify that the host cell expression system plays a modulatory role in TRPV1 receptor activity, and suggests that activation of native human TRPV1 receptors in vivo will be dependent on cell-specific regulatory factors/pathways.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. bruce.bianchi@abbott.com
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bianchi
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Rachid
authors.initials: R
authors.lastname: El Kouhen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Moreland
authors.forename: Connie R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Puttfarcken
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011522:Protons; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D011522:Protons; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002118:Calcium