Nonivamide, a capsaicin analog, increases dopamine and serotonin release in SH-SY5Y cells via a TRPV1-independent pathway.
METHODS
Dietary intake of capsaicin has been shown to reduce body weight by increasing energy expenditure, and to enhance alertness and mood by stimulating the brain's reward system. Binding of capsaicin to the vanilloid receptor 1 (transient receptor potential cation channel subfamily V member 1 (TRPV1)) is one of the major cellular mechanisms responsible for these effects. However, strong TRPV1 agonists like capsaicin elicit a sharp, burning pain that limits their dietary intake. The present study aimed to investigate the effect of the less pungent capsaicin-analog nonivamide on dopamine and serotonin release in neural SH-SY5Y cells.


RESULTS
Nonivamide (1 μM) stimulated the Ca(2+) -dependent release of serotonin (272 ± 115%) and dopamine (646 ± 48%) in SH-SY5Y cells compared to nontreated cells (100%) to a similar extent as capsaicin. qRT-PCR analysis of 1 μM nonivamide-treated SH-SY5Y cells revealed gene regulation of the receptors dopamine D1 and D2, serotonin HTR1A, 1B and 2A, cannabinoid 1, and TRPV1. Co-incubation experiments of SH-SY5Y cells with the TRPV1 inhibitors trans-tert-butylcyclohexanol and capsazepine demonstrated that capsaicin, but not nonivamide, induces serotonin and dopamine release through TRPV1 activation.


CONCLUSIONS
The results indicate a TRPV1-independent signaling pathway for nonivamide that might allow dietary administration of higher doses of nonivamide compared to capsaicin.
Christian Doppler Laboratory for Bioactive Aroma Compounds, University of Vienna, Vienna, Austria.
Barbara
B
Rohm
Ann-Katrin
AK
Holik
Mark M
MM
Somoza
Marc
M
Pignitter
Mathias
M
Zaunschirm
Jakob P
JP
Ley
Gerhard E
GE
Krammer
Veronika
V
Somoza
D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003511:Cyclohexanols / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D018689:Sensory System Agents / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
D003511:Cyclohexanols; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D012701:Serotonin; C557786:4-tert-butylcyclohexanol; C071423:capsazepine; D002211:Capsaicin; C040937:nonivamide; D004298:Dopamine
Capsaicin; Dopamine; Nonivamide; Serotonin; TRPV1