Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Involvement of D2 Receptor on Dopamine-induced Action in Interstitial Cells of Cajal from Mouse Colonic Intestine

  • Zuoa, Dong Chuan (Department of Physiology, College of Medicine, Chosun University) ;
  • Shahia, Pawan Kumar (Department of Physiology, College of Medicine, Chosun University) ;
  • Choia, Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Jun, Jae-Yeoul (Department of Physiology, College of Medicine, Chosun University) ;
  • Park, Jong-Seong (Department of Physiology, Chonnam National University Medical School)
  • Received : 2012.07.16
  • Accepted : 2012.08.07
  • Published : 2012.09.30
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Abstract

Dopamine is an enteric neurotransmitter that regulates gastrointestinal motility. This study was done to investigate whether dopamine modulates spontaneous pacemaker activity in cultured interstitial cells of Cajal (ICCs) from mouse using whole cell patch clamp technique, RT-PCR and live $Ca^{2+}$ imaging analysis. ICCs generate pacemaker inward currents at a holding potential of -70 mV and generate pacemaker potentials in current-clamp mode. Dopamine did not change the frequency and amplitude of pacemaker activity in small intestinal ICCs. On the contrary dopamine reduced the frequency and amplitude of pacemaker activity in large intestinal ICCs. RT-PCR analysis revealed that Dopamine2 and 4-receptors are expressed in c-Kit positive ICCs. Dopamine2 and 4 receptor agonists inhibited pacemaker activity in large intestinal ICCs mimicked those of dopamine. Domperidone, dopamine2 receptor antagonist, increased the frequency of pacemaker activity of large intestinal ICCs. In $Ca^{2+}$-imaging, dopamine inhibited spontaneous intracellular $Ca^{2+}$ oscillations of ICCs. These results suggest that dopamine can regulate gastrointestinal motility through modulating pacemaker activity of large intestinal ICCs and dopamine effects on ICCs are mediated by dopamine2 receptor and intracellular $Ca^{2+}$ modulation.

Keywords

References

  1. Abe M, Orita Y, Nakashima Y, Nakamura M. Hypertensive crisis induced by metocloprimed in patient with pheochromocytoma. Angiology. 1984. 35: 122-128. https://doi.org/10.1177/000331978403500209
  2. Adler-Graschinsky E, Rubio MC, Barontini De Moyano M. Metoclopramide increases the release of catecholamines from isolated human phaeochromocytomas. J Hypertens. 1984. 2: 127-129. https://doi.org/10.1097/00004872-198404000-00002
  3. Eaker EY, Bixler GB, Dunn AJ, Moreshead WV, Mathias JR. Dopamine and norepinephrine in the gastrointestinal tract of mice and the effects of neurotoxins. J Pharmcol Exp Ther. 1988. 244: 438-442.
  4. Gershon MD. Inhibition of gastrointestinal movement by sympathetic nerve stimulation: the site of action. J Physiol (Lond). 1967. 198: 317-329.
  5. Grivegnee AR, Fontaine J, Reuse J. Effect of dopamine on dog distal colon in-vitro. J Pharm Pharmacol. 1984. 36: 454-457. https://doi.org/10.1111/j.2042-7158.1984.tb04424.x
  6. Hartman DS, Civelli O. Dopamine receptor diversity: molecular and pharmacological perspectives. Prog Drug Res. 1997. 48: 173-194.
  7. Hirst GD, Silinsky EM. Some effects of 5-hydroxytryptamine, dopamine and noradrenaline on neurons in the submucous plexus of guinea-pig small intestine. J Physiol (Lond). 1975. 251: 817-832.
  8. Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebocontrolled trial of itopride in functional dyspepsia. N Engl J Med. 2006. 354: 832-840. https://doi.org/10.1056/NEJMoa052639
  9. Huisinga J. Physiology and pathophysiology of interstitial cells of Cajal: from bench to bedside. II. Gastric motility lessons from mutant mice on slow waves and innervation. Am J Physiol. 2001. 281: G1129-G1134.
  10. Iwanaga Y, Kimura T, Miyashita N, Morikawa K, Nagata O, Itoh Z, Kondo Y. Characterization of acetylcholinesterase-inhibition by itopride. Jpn J Pharmacol. 1994. 66: 317-322. https://doi.org/10.1254/jjp.66.317
  11. Iwanaga Y, Miyashita N, Morikawa K, Mizumoto A, Kondo Y, Itoh Z. A novel water-soluble dopamine-2 antagonist with anticholinesterase activity in gastrointestinal motor activity. Gastroenterology. 1990. 99: 401-408.
  12. Iwanaga Y, Miyashita N, Saito T, Morikawa K, Itoh Z. Gastroprokinetic effect of a new benzamide derivative itopride and its action mechanisms in conscious dogs. Jpn J Pharmacol. 1996. 71: 129-137. https://doi.org/10.1254/jjp.71.129
  13. Ji SW, Park JH, Cho JS, Lim JH, Lee SI. Investigation into the effects of mosapride on motility of Guinea pig stomach, ileum, and colon. Yonsei Med J. 2003. 44: 653-664.
  14. Jun JY, Choi S, Yeum CH, Chang IY, Park CK, Kim MY, Kong ID, So I, Kim KW, You HJ. Noradrenaline inhibits pacemaker currents through stimulation of b1-adrenoceptors in cultured interstitial cells of Cajal from murine small intestine. Br J Pharmacol. 2004. 141: 670-677. https://doi.org/10.1038/sj.bjp.0705665
  15. Li ZS, Schmauss C, Cuenca A, Ratcliffe E, Gershon MD. Physiological modulation of intestinal motility by enteric dopaminergic neurons and the $D_{2}$ receptor: analysis of dopamine receptor expression, location, development, and function in wild-type and knock-out mice. J Neurosci. 2006. 26: 2798-2807. https://doi.org/10.1523/JNEUROSCI.4720-05.2006
  16. Lucchelli A, Boselli C, Chiari MC, Grana E. Analysis of the relaxing effect of dopamine on the isolated rat jejunum. Arch Int Pharmacodyn Ther. 1986. 279: 234-247.
  17. Lucchelli A, Boselli C, Grana E. Dopamine-induced relaxation of the guinea-pig isolated jejunum is not mediated through dopamine receptors. Pharmacol Res. 1990. 2: 433-444.
  18. Mine Y, Yoshikawa T, Oku S, Nagai R, Yoshida H, Hosoki K. Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonist on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther. 1997. 283: 1000-1008.
  19. Sakaguchi J, Nishino H, Ogawa N, Iwanaga Y, Yasuda S, Kato H, Ito Y. Synthesis, gastrointestinal prokinetic activity and structure-activity relationships of novel N-[[2-(dialkylamino)-ethoxy]bexzyl]benzamide derivatives. Chem Pharm Bull. 1992. 40: 202-211. https://doi.org/10.1248/cpb.40.202
  20. Sanders KM. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology. 1996. 111: 492-515. https://doi.org/10.1053/gast.1996.v111.pm8690216
  21. Scheibner J, Trendelenburg AU, HeIN L, Starke K, Blandizzi C. Alpha 2 adrenoceptors in the enteric nervous system: a study in alpha 2A-adrenoceptor-deficient mice. Br J Pharmacol. 2002. 135: 697-704. https://doi.org/10.1038/sj.bjp.0704512
  22. Scratcherd T, Grundy D. The physiology of intestinal motility and secretion. Br J Anaesth. 1984. 56: 3-18. https://doi.org/10.1093/bja/56.1.3
  23. 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
  24. 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
  25. Tan S, Hermann B, Borrelli E. Dopaminergic mouse mutants: investigating the roles of the different dopamine receptor subtypes and the dopamine transporter. Int Rev Neurobiol. 2003. 54: 145-197.
  26. Torihashi S, Horisawa M, Watanabe Y. c-Kit immunoreactive interstitial cells in the human gastrointestinal tract. J Auton Nerv Syst. 1999. 75: 38-50. https://doi.org/10.1016/S0165-1838(98)00174-X
  27. Tsai LH, Cheng JT. The effect of exogenous dopamine on ileal smooth muscle of guinea-pigs. Chin J Physiol. 1992. 35: 133-141.
  28. Van Nueten JM, Schuurkes AJ. Studies on the role of dopamine and dopamine blockers in gastroduodenal motility. Scand Gastroenterol Suppl. 1984. 96: 89-99.
  29. Ward S. Interstitial cells of Cajal in enteric neurotransmission. Gut. 2000. 47: 40-43.
  30. 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