Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
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Shengmaisan Regulates Pacemaker Potentials in Interstitial Cells of Cajal in Mice

  • Kim, Byung Joo (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine)
  • Received : 2013.09.10
  • Accepted : 2013.11.03
  • Published : 2013.12.31
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Abstract

Objectives: Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of diverse organs in Korea. The interstitial cells of Cajal (ICCs) are pacemaker cells that play an important role in the generation of coordinated gastrointestinal (GI) motility. We have aimed to investigate the effects of SMS in the ICCs in the mouse small intestine. Methods: To dissociate the ICCs, we used enzymatic digestions from the small intestine in a mouse. After that, the ICCs were identified immunologically by using the anti-c-kit antibody. In the ICCs, the electrophysiological whole-cell patch-clamp configuration was used to record pacemaker potentials in the cultured ICCs. Results: The ICCs generated pacemaker potentials in the mouse small intestine. SMS produced membrane depolarization with concentration-dependent manners in the current clamp mode. Pretreatment with a $Ca^{2+}$ free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, stopped the generation of the pacemaker potentials. In the case of $Ca^{2+}$-free solutions, SMS induced membrane depolarizations. However, when thapsigargin in a bath solution was applied, the membrane depolarization was not produced by SMS. The membrane depolarizations produced by SMS were inhibited by U-73122, an active phospholipase C (PLC) inhibitors. Furthermore, chelerythrine and calphostin C, a protein kinase C (PKC) inhibitors had no effects on SMS-induced membrane depolarizations. Conclusions: These results suggest that SMS might affect GI motility by modulating the pacemaker activity through an internal $Ca^{2+}$- and PLC-dependent and PKC-independent pathway in the ICCs.

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References

  1. Cheng JT. Review: drug therapy in Chinese traditional medicine. J Clin Pharmacol. 2000;40(5):445-50. https://doi.org/10.1177/00912700022009198
  2. Xu N, Qiu C, Wang W, Wang Y, Chai C, Yan Y, et al. HPLC/MS/MS for quantification of two types of neurotransmitters in rat brain and application: myocardial ischemia and protection of Sheng-Mai-San. J Pharm Biomed Anal. 2011;55(1):101-8. https://doi.org/10.1016/j.jpba.2010.12.015
  3. Nishida H, Kushida M, Nakajima Y, Ogawa Y, Tatewaki N, Sato S, et al. Amyloid-$\beta$-induced cytotoxicity of PC- 12 cell was attenuated by Shengmai-san through redox regulation and outgrowth induction. J Pharmacol Sci. 2007;104(1):73-81. https://doi.org/10.1254/jphs.FP0070100
  4. Wang NL, Chang CK, Liou YL, Lin CL, Lin MT. Shengmai San, a Chinese herbal medicine protects against rat heat stroke by reducing inflammatory cytokines and nitric oxide formation. J Pharmacol Sci. 2005;98(1):1-7. https://doi.org/10.1254/jphs.FP0050018
  5. Ward SM, Burns AJ, Torihashi S, Sanders KM. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994;480(Pt 1):91-7. https://doi.org/10.1113/jphysiol.1994.sp020343
  6. Huizinga JD, Thuneberg L, Klüppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373(6512):347-9. https://doi.org/10.1038/373347a0
  7. Sanders KM. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology. 1996;111(2):492-515. https://doi.org/10.1053/gast.1996.v111.pm8690216
  8. Gfroerer S, Rolle U. Interstitial cells of Cajal in the normal human gut and in Hirschsprung disease. Pediatr Surg Int. 2013;29(9):889-97. https://doi.org/10.1007/s00383-013-3364-y
  9. Won KJ, Sanders KM, Ward SM. Interstitial cells of Cajal mediate mechanosensitive responses in the stomach. Proc Natl Acad Sci U S A. 2005;102(41):14913-8. https://doi.org/10.1073/pnas.0503628102
  10. Kim BJ, Lim HH, Yang DK, Jun JY, Chang IY, Park CS, et al. Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity. Gastroenterology. 2005;129(5):1504-17. https://doi.org/10.1053/j.gastro.2005.08.016
  11. Koh SD, Sanders KM, Ward SM. Spontaneous electrical rhythmicity in cultured interstitial cells of Cajal from the murine small intestine. J Physiol. 1998;513(Pt 1):203-13. https://doi.org/10.1111/j.1469-7793.1998.203by.x
  12. Ward SM, Ordog T, Koh SD, Baker SA, Jun JY, Amberg G, et al. Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. J Physiol. 2000;525(Pt 2):355-61. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00355.x
  13. Choi S, Choi JJ, Jun JY, Koh JW, Kim SH, Kim DH, et al. Induction of pacemaker currents by DA-9701, a prokinetic agent, in interstitial cells of Cajal from murine small intestine. Mol Cells. 2009;27(3):307-12. https://doi.org/10.1007/s10059-009-0039-6
  14. Sakamoto T, Unno T, Matsuyama H, Uchiyama M, Hattori M, Nishimura M, et al. Characterization of muscarinic receptor-mediated cationic currents in longitudinal smooth muscle cells of mouse small intestine. J Pharmacol Sci. 2006;100(3):215-26. https://doi.org/10.1254/jphs.FP0050973
  15. Aiello EA, Clement-Chomienne O, Sontag DP, Walsh MP, Cole WC. Protein kinase C inhibits delayed rectifier $K^{+}$ current in rabbit vascular smooth muscle cells. Am J Physiol. 1996;271(1 Pt 2):H109-19.
  16. Ichikawa H, Wang L, Konishi T. Prevention of cerebral oxidative injury by post-ischemic intravenous administration of Shengmai San. Am J Chin Med. 2006;34(4):591-600. https://doi.org/10.1142/S0192415X06004120
  17. Ichikawa H, Wang X, Konishi T. Role of component herbs in antioxidant activity of shengmai San-a traditional Chinese medicine formula preventing cerebral oxidative damage in rat. Am J Chin Med. 2003;31(4):509-21. https://doi.org/10.1142/S0192415X03001193
  18. Wang L, Nishida H, Ogawa Y, Konishi T. Prevention of oxidative injury in PC12 cells by a traditional Chinese medicine, Shengmai San, as a model of an antioxidant- based composite formula. Biol Pharm Bull. 2003;26(7):1000-4. https://doi.org/10.1248/bpb.26.1000
  19. You JS, Huang HF, Chang YL, Lee YS. Sheng-Mai-San reduces adriamycin-induced cardiomyopathy in rats. Am J Chin Med. 2006;34(2):295-305. https://doi.org/10.1142/S0192415X06003849
  20. Fang J, Jiang J, Luo DC. Effect of Shengmai San oral fluid on coronary arteriosclerotic. Chin Med J. 1987;26:403-9.
  21. Zhao MH, Rong YZ, Lu BJ. Effect of Shengmai San on serum lipid peroxidation in acute viral myocarditis. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1996;16:142-5.
  22. Hagger R, Gharaie S, Finlayson C, Kumar D. Distribution of the interstitial cells of Cajal in the human anorectum. J Auton Nerv Syst. 1998;73(2-3):75-9. https://doi.org/10.1016/S0165-1838(98)00038-1
  23. Faussone-Pellegrini MS, Cortesini C. Ultrastructural features and localization of the interstitial cells of Cajal in the smooth muscle coat of human esophagus. J Submicrosc Cytol. 1985;17(2):187-97.
  24. Torihashi S, Horisawa M, Watanabe Y. C-kit immunoreactive interstitial cells in the human gastrointestinal tract. J Auton Nerv Syst. 1999;75(1):38-50 https://doi.org/10.1016/S0165-1838(98)00174-X

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