Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1.
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.
Tóth
Attila
A
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.
Wang
Yun
Y
Kedei
Noémi
N
Tran
Richard
R
Pearce
Larry V
LV
Kang
Sang-Uk
SU
Jin
Mi-Kyung
MK
Choi
Hyun-Kyung
HK
Lee
Jeewoo
J
Blumberg
Peter M
PM
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
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