title: Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1.
abstract: The vanilloid receptor subtype 1 (TRPV1 or VR1) is expressed in nociceptive primary afferents of the C-fiber 'pain' pathway and has attracted considerable attention as a therapeutic target. Here, using rat TRPV1 heterologously expressed in Chinese hamster ovary cells, we show that different agonists show different patterns of modulation of the intracellular Ca2+ concentration, monitored in individual cells by fura-2 Ca2+ imaging. We identified 5 parameters (potency, maximal response, latency of response, variability of latency of response among individual cells, and desensitization) which behaved differently for different compounds. The potencies of the compounds examined ranged from EC50 values of 80 pM to 9 microM. Peak levels of induced [Ca2+]i were observed either higher (RTX) or lower (anandamide) than for capsaicin. Significant latencies of response were observed for some (e.g. RTX) but not other derivatives, with great variation among individual cells in this latency. Marked desensitization after stimulation was detected in some cases (e.g. anandamide, capsaicin); for others, no desensitization was observed. We conclude that structurally diverse vanilloid agonists induce marked diversity in the patterns of Ca2+ response. This diversity of response may provide opportunities for pharmacological exploitation.
authors.affiliation: Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bldg. 37, Room 4048, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-4255, United States.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Noémi
authors.initials: N
authors.lastname: Kedei
authors.forename: Richard
authors.initials: R
authors.lastname: Tran
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Kang
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Jin
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Choi
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002211:Capsaicin / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000378:metabolism*; D063388:Endocannabinoids; D005456:Fluorescent Dyes; D016257:Fura-2; D007473:Ion Channels / Q000819:agonists* / Q000378:metabolism*; D007700:Kinetics; D053284:Polyunsaturated Alkamides; D051381:Rats; D050916:TRPV Cation Channels
chemical_list: D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D004224:Diterpenes; D063388:Endocannabinoids; D005456:Fluorescent Dyes; D007473:Ion Channels; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C024353:resiniferatoxin; D002211:Capsaicin; D002118:Calcium; D016257:Fura-2; C078814:anandamide