The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

  • Shahi, Pawan Kumar (Department of Physiology, College of Medicine, Chosun University) ;
  • Choi, Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Zuo, Dong Chuan (Department of Physiology, College of Medicine, Chosun University) ;
  • Yeum, Cheol-Ho (Department of Physiology, College of Medicine, Chosun University) ;
  • Yoon, Pyung-Jin (Department of Physiology, College of Medicine, Chosun University) ;
  • Lee, Jun (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Kim, Young-Dae (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Park, Chan-Guk (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Kim, Man-Yoo (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Shin, Hye-Rang (Department of Psychiatry, College of Medicine, Chosun University) ;
  • Oh, Hyun-Jung (Department of Psychiatry, College of Medicine, Chosun University) ;
  • Jun, Jae-Yeoul (Department of Physiology, College of Medicine, Chosun University)
  • Received : 2011.04.08
  • Accepted : 2011.06.14
  • Published : 2011.06.30
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Abstract

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-$HT_{2B,\;3,\;4,\;and\;7}$ receptors in ICC. However, SDZ 205557 (a 5-$HT_4$ receptor antagonist), SB 269970 (a 5-$HT_7$ receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-$HT_3$ antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-$HT_{2B}$ receptor antagonist). Based on $[Ca^{2+}]_i$ analysis, we found that 5-HT increased the intensity of $[Ca^{2+}]_i$. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-$HT_{3,\;4,\;and\;7}$ receptors via $[Ca^{2+}]_i$ mobilization and regulation of mitogen-activated protein kinases.

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References

  1. Ward SM, Burns AJ, Torihashi S, Harney SC, Sanders KM. Impaired development of interstitial cells and intestinal electrical rhythmicity in steel mutants. Am J Physiol. 1995;269:C1577-1585. https://doi.org/10.1152/ajpcell.1995.269.6.C1577
  2. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373:347-349. https://doi.org/10.1038/373347a0
  3. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38:1083-1152. https://doi.org/10.1016/S0028-3908(99)00010-6
  4. Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav. 2002;71:533-554. https://doi.org/10.1016/S0091-3057(01)00746-8
  5. Zhu JX, Zhu XY, Owyang C, Li Y. Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat. J Physiol. 2001;530:431-442. https://doi.org/10.1111/j.1469-7793.2001.0431k.x
  6. Fiorica-Howells E, Maroteaux L, Gershon MD. Serotonin and the 5-HT(2B) receptor in the development of enteric neurons. J Neurosci. 2000;20:294-305.
  7. Nebigil CG, Etienne N, Messaddeq N, Maroteaux L. Serotonin is a novel survival factor of cardiomyocytes: mitochondria as a target of 5-$HT_{2B}$ receptor signaling. FASEB J. 2003;17:1373-1375. https://doi.org/10.1096/fj.02-1122fje
  8. Baker DE. Rationale for using serotonergic agents to treat irritable bowel syndrome. Am J Health Syst Pharm. 2005;62:700-711.
  9. Hansen MB, Skadhauge E. Signal transduction pathways for serotonin as an intestinal secretagogue. Comp Biochem Physiol A Physiol. 1997;118:283-290. https://doi.org/10.1016/S0300-9629(97)00085-6
  10. Jin JG, Foxx-Orenstein AE, Grider JR. Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-$HT_{4}$ and 5-$HT_{3}$ receptors. J Pharmacol Exp Ther. 1999;288:93-97.
  11. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397-414. https://doi.org/10.1053/j.gastro.2006.11.002
  12. Read NW, Gwee KA. The importance of 5-hydroxytryptamine receptors in the gut. Pharmacol Ther. 1994;62:159-173. https://doi.org/10.1016/0163-7258(94)90009-4
  13. Wouters MM, Gibbons SJ, Roeder JL, Distad M, Ou Y, Strege PR, Szurszewski JH, Farrugia G. Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors. Gastroenterology. 2007;133:897-906. https://doi.org/10.1053/j.gastro.2007.06.017
  14. Beattie DT, Smith JA. Serotonin pharmacology in the gastrointestinal tract: a review. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:181-203. https://doi.org/10.1007/s00210-008-0276-9
  15. Epperson A, Hatton WJ, Callaghan B, Doherty P, Walker RL, Sanders KM, Ward SM, Horowitz B. Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol Cell Physiol. 2000;279:C529-539. https://doi.org/10.1152/ajpcell.2000.279.2.C529
  16. Glatzle J, Sternini C, Robin C, Zittel TT, Wong H, Reeve JR Jr, Raybould HE. Expression of 5-$HT_{3}$ receptors in the rat gastrointestinal tract. Gastroenterology. 2002;123:217-226. https://doi.org/10.1053/gast.2002.34245
  17. De Ponti F. Pharmacology of serotonin: what a clinician should know. Gut. 2004;53:1520-1535. https://doi.org/10.1136/gut.2003.035568
  18. Gershon MD. Review article: serotonin receptors and transporters -- roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther. 2004;20 Suppl 7:3-14.
  19. Buchheit KH, Buhl T. Stimulant effects of 5-hydroxytryptamine on guinea pig stomach preparations in vitro. Eur J Pharmacol. 1994;262:91-97. https://doi.org/10.1016/0014-2999(94)90031-0
  20. Xue L, Camilleri M, Locke GR 3rd, Schuurkes JA, Meulemans A, Coulie BJ, Szurszewski JH, Farrugia G. Serotonergic modulation of murine fundic tone. Am J Physiol Gastrointest Liver Physiol. 2006;291:G1180-1186. https://doi.org/10.1152/ajpgi.00224.2006
  21. Ward SM, Ordog T, Koh SD, Baker SA, Jun JY, Amberg G, Monaghan K, Sanders KM. Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. J Physiol. 2000;525:355-361. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00355.x
  22. Suzuki H, Takano H, Yamamoto Y, Komuro T, Saito M, Kato K, Mikoshiba K. Properties of gastric smooth muscles obtained from mice which lack inositol trisphosphate receptor. J Physiol. 2000;525:105-111. https://doi.org/10.1111/j.1469-7793.2000.00105.x
  23. Aoyama M, Yamada A, Wang J, Ohya S, Furuzono S, Goto T, Hotta S, Ito Y, Matsubara T, Shimokata K, Chen SR, Imaizumi Y, Nakayama S. Requirement of ryanodine receptors for pacemaker $Ca^{2+}$ activity in ICC and HEK293 cells. J Cell Sci. 2004;117:2813-2825. https://doi.org/10.1242/jcs.01136
  24. Choi S, Yeum CH, Chang IY, You HJ, Park JS, Jeong HS, So I, Kim KW, Jun JY. Activating of ATP-dependent $K^{+}$ channels comprised of K(ir) 6.2 and SUR 2B by $PGE_{2}$ through $EP_{2}$ receptor in cultured interstitial cells of Cajal from murine small intestine. Cell Physiol Biochem. 2006;18:187-198. https://doi.org/10.1159/000097516
  25. So KY, Kim SH, Sohn HM, Choi SJ, Parajuli SP, Choi S, Yeum CH, Yoon PJ, Jun JY. Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine. Mol Cells. 2009;27:525-531. https://doi.org/10.1007/s10059-009-0076-1
  26. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153-183. https://doi.org/10.1210/er.22.2.153
  27. Errico M, Crozier RA, Plummer MR, Cowen DS. 5-HT(7) receptors activate the mitogen activated protein kinase extracellular signal related kinase in cultured rat hippocampal neurons. Neuroscience. 2001;102:361-367. https://doi.org/10.1016/S0306-4522(00)00460-7
  28. Machida T, Ohta M, Onoguchi A, Iizuka K, Sakai M, Minami M, Hirafuji M. 5-Hydroxytryptamine induces cyclooxygenase-2 in rat vascular smooth muscle cells: mechanisms involving Src, PKC and MAPK activation. Eur J Pharmacol. 2011;656:19-26. https://doi.org/10.1016/j.ejphar.2010.12.044
  29. Park CG, Kim YD, Kim MY, Koh JW, Jun JY, Yeum CH, So I, Choi S. Effects of prostaglandin $F_{2_{\alpha}}$ on small intestinal interstitial cells of Cajal. World J Gastroenterol. 2011;17:1143-1151. https://doi.org/10.3748/wjg.v17.i9.1143

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