Abstract
Our recent study found that TRPA1 is highly expressed in enterochromaffin cells and that stimulation of these cells with TRPA1 agonists enhances 5-hydroxytryptamine (5-HT) secretion in vitro. Here, to demonstrate the 5-HT-releasing effect of TRPA1 agonists in vivo, we examined the effect of TRPA1 agonists on gastric emptying in rats. The results showed that TRPA1 agonists dose-dependently delayed gastric emptying. Further, the effects of TRPA1 agonists on this delay were abolished in rats treated with a TRPA1 antagonist, an inhibitor of tryptophan hydroxylase, or a 5-HT3 receptor antagonist. Taken together, these results indicate that TRPA1 agonists delay in vivo gastric emptying through serotonergic pathways.
References
Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM (2007) Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol 583(Pt 1):175–193
Andrade EL, Luiz AP, Ferreira J, Calixto JB (2008) Pronociceptive response elicited by TRPA1 receptor activation in mice. Neuroscience 152(2):511–520
Ballinger A, El-Haj T, Perrett D, Turvill J, Obeid O, Dryden S, Williams G, Farthing MJ (2000) The role of medial hypothalamic serotonin in the suppression of feeding in a rat model of colitis. Gastroenterology 118(3):544–553
Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41(6):849–857
Bang S, Kim KY, Yoo S, Kim YG, Hwang SW (2007) Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci 26(9):2516–2523
Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124(6):1269–1282
Braun T, Voland P, Kunz L, Prinz C, Gratzl M (2007) Enterochromaffin cells of the human gut: sensors for spices and odorants. Gastroenterology 132(5):1890–1901
Cortright DN, Krause JE, Broom DC (2007) TRP channels and pain. Biochim Biophys Acta 1772(8):978–988
Gershon MD (2003) Plasticity in serotonin control mechanisms in the gut. Curr Opin Pharmacol. 3(6):600–607
Gershon MD, Tack J (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132(1):397–414
Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427(6971):260–265
Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Sakagami M, Noguchi K (2006) Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol 200(1):112–123
Kushnir-Sukhov NM, Brittain E, Scott L, Metcalfe DD (2008) Clinical correlates of blood serotonin levels in patients with mastocytosis. Eur J Clin Invest 38(12):953–8
Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50(2):277–289
Lee SP, Buber MT, Yang Q, Cerne R, Cortes RY, Sprous DG, Bryant RW (2008) Thymol and related alkyl phenols activate the hTRPA1 channel. Br J Pharmacol 153(8):1739–1749
Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S, Sano Y, Inamura K, Matsushime H, Koizumi T, Yokoyama T, Ito H (2009) TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci U S A 106(9):3408–3413
Prasad P, Yanagihara AA, Small-Howard AL, Turner H, Stokes AJ (2008) Secretogranin III directs secretory vesicle biogenesis in mast cells in a manner dependent upon interaction with chromogranin A. J Immunol 181(7):5024–5034
Ringvall M, Ronnberg E, Wernersson S, Duelli A, Henningsson F, Abrink M, Garcia-Faroldi G, Fajardo I, Pejler G (2008) Serotonin and histamine storage in mast cell secretory granules is dependent on serglycin proteoglycan. J Allergy Clin Immunol 121(4):1020–1026
Ruparel NB, Patwardhan AM, Akopian AN, Hargreaves KM (2008) Homologous and heterologous desensitization of capsaicin and mustard oil responses utilize different cellular pathways in nociceptors. Pain 135(3):271–279
Sharma M, Rai K, Sharma SS, Gupta YK (2000) Effect of antioxidants on pyrogallol-induced delay in gastric emptying in rats. Pharmacology 60(2):90–96
Spiller R (2007) Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease. Neurogastroenterol Motil 19(Suppl 2):25–31
St Pierre M, Reeh PW, Zimmermann K (2009) Differential effects of TRPV channel block on polymodal activation of rat cutaneous nociceptors in vitro. Exp Brain Res 196(1):31–44
Tominaga M, Caterina MJ (2004) Thermosensation and pain. J Neurobiol 61(1):3–12
Wingren U, Enerback L, Ahlman H, Allenmark S, Dahlstrom A (1983) Amines of the mucosal mast cell of the gut in normal and nematode infected rats. Histochemistry 77(2):145–158
Yamano M, Kamato T, Nagakura Y, Miyata K (1997) Effects of gastroprokinetic agents on gastroparesis in streptozotocin-induced diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 356(1):145–150
Yu S, Gao G, Peterson BZ, Ouyang A (2009) TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C fibers in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol 297(1):G34–G42
Acknowledgements
We would like to thank T. Koizumi, M. Yamano, Y. Takinami, R. Takezawa, Y. Takemoto, T. Goto, H. Tanaka, H. Okada, H. Kamada, and M. Okada for their excellent technical assistance and advice.
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Doihara, H., Nozawa, K., Kawabata-Shoda, E. et al. TRPA1 agonists delay gastric emptying in rats through serotonergic pathways. Naunyn-Schmied Arch Pharmacol 380, 353–357 (2009). https://doi.org/10.1007/s00210-009-0435-7
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DOI: https://doi.org/10.1007/s00210-009-0435-7