Nonivamide, a capsaicin analog, increases dopamine and serotonin release in SH-SY5Y cells via a TRPV1-independent pathway

• Published in: Molecular nutrition & food research 2013-11, Vol.57 (11), p.2008-2018
• Main Authors: Rohm, Barbara, Holik, Ann-Katrin, Somoza, Mark M., Pignitter, Marc, Zaunschirm, Mathias, Ley, Jakob P., Krammer, Gerhard E., Somoza, Veronika
• Format: Article
• Language: English
• Subjects: Analgesics; Biological and medical sciences; Capsaicin; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Cyclohexanols - pharmacology; Dopamine; Dopamine - metabolism; Dose-Response Relationship, Drug; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; Medical sciences; Neuropharmacology; Nonivamide; Pharmacology. Drug treatments; Sensory System Agents - pharmacology; Serotonin; Serotonin - metabolism; Signal Transduction; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; TRPV1; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201200846

Scope 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. Methods and results Nonivamide (1 μM) stimulated the Ca2+‐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. Conclusion The results indicate a TRPV1‐independent signaling pathway for nonivamide that might allow dietary administration of higher doses of nonivamide compared to capsaicin.