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The Effect of Rebamipide on the Regulation of Intestinal Contractility

Carbachol에 의한 위장관 수축에 대한 rebamipide의 융합성 조절 효과

  • Je, Hyun Dong (Dept. of Pharmacology, College of Pharmacy, Daegu Catholic University) ;
  • Min, Young Sil (Dept. of Pharmaceutical Science, Jungwon University)
  • 제현동 (대구가톨릭대학교 약학대학 약학과) ;
  • 민영실 (중원대학교 제약공학과)
  • Received : 2020.09.06
  • Accepted : 2020.10.20
  • Published : 2020.10.28

Abstract

The aim of the study was to observe the influence and related mechanism of rebamipide on the intestinal contraction. Intestinal contraction includes the activation of thick or thin filament regulation. However, there are few reports addressing the question whether this regulation is involved in rebamipide-induced regulation. We hypothesized that rebamipide plays a role in intestinal contraction evoked by carbachol in rat intestine. Interestingly, rebamipide alone didn't inhibit and rather slightly increased the contraction in the denuded muscle. Therefore, rebamipide alone and together with indomethacin increases the ileal contraction suggesting that additional pathways might be involved in the regulation of ileal contractility. In conclusion, rebamipide has some effect on the regulation of contractility and anti-ulcer by NSAIDs.

이번 연구는 소화기계 출혈, 궤양 등에 대해 치료와 예방을 목적으로 사용되는 rebamipide에서 농도 의존적 장관 수축성 조절 기전에 대해 조사하고자 한다. 소화기 수축은 근육의 섬유의 조절에 의하여 일어난다. 실험용 쥐의 회장 과 결장을 적출하여 carbachol로 회장 과 결장의 근육수축을 유발하여 연구를 진행하였다. rebamipide 단독으로 장관수축을 억제하지 않고 소폭으로 carbachol 유도 수축을 높이는 것으로 관찰되었다. 소화기계 부작용을 일으키는 indomethacin 과 rebamipide를 흔히 병용하기에, 병용 효과를 관찰하였다. Indomethacin과 병용된 rebamipide는 장관 중 회장의 수축성을 증대시켰다. rebamipide는 장관중 회장에서 수축성을 증대시키고, NSAIDs에 의한 궤양에 대한 항궤양효과 외에 운동성도 일부 조절하는 것으로 생각된다.

Keywords

References

  1. K. M. Sanders, S. J. Hwang & S. M. Ward. (2010). Neuroeffector apparatus in gastrointestinal smooth muscle organs. J. Physiol, 588(Pt23), 4621-4639. DOI: 10.1113/jphysiol.2010.196030
  2. M. Kurahashi et al. (2011). A functional role for the 'fibroblast-like cells' in gastrointestinal smooth muscles. J. Physiol, 589(Pt3), 697-710. DOI : 10.1113/jphysiol.2010.201129
  3. R. C. Webb. (2003). Smooth muscle contraction and relaxation. Adv. Physiol. Educ, 27(1-4), 201-206. DOI : 10.1152/advan.00025.2003
  4. T. Yoshikawa et al. (1993). Free radical scavenging activity of the novel anti-ulcer agent rebamipide studied by electron spin resonance. Arzneimittelforschung, 43(3), 363-366. https://pubmed.ncbi.nlm.nih.gov/8387788/
  5. Y. Naito et al. (1995). Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study. Free. Radic. Biol. Med, 18(1), 117-123. DOI : 10.1016/0891-5849(94)00110-6
  6. H. D. Je, J. M. Lee & H. O. La. (2010). The Inhibitory Effect of Eupatilin on the Intestinal Contraction Induced by Carbachol. Biomol. & Thera, 18(4), 442-447. DOI : 10.4062/biomolther.2010.18.4.442
  7. Y. J. Xiong et al. (2013). The characteristics of genistin-induced inhibitory effects on intestinal motility. Arch. Pharm. Res, 36(3), 345-352. DOI : 10.1007/s12272-013-0053-2
  8. W. Q. He et al. (2013). Altered Contractile Phenotypes of Intestinal Smooth Muscle in Mice Deficient in Myosin Phosphatase Target Subunit 1. Gastroenterology, 144(7), 1456-1465. DOI : 10.1053/j.gastro.2013.02.045
  9. A. P. Somlyo & A. V. Somlyo. (1994). Signal transduction and regulation in smooth muscle. Nature, 372(6503), 231-236. DOI : 10.1038/372231a0
  10. A. P. Somlyo & A. V. Somlyo. (1998). From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta. Physiol. Scand, 164(4), 437-448. DOI : 10.1046/j.1365-201X.1998.00454.x
  11. M. Uehata et al. (1997). Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature, 389(6654), 990-994. DOI : 10.1038/40187
  12. S. Sakurada et al. (2003). $Ca^{2+}$-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res, 93(6), 548-556. DOI : 10.1161/01.RES.0000090998.08629.60
  13. T. Kitazawa, M. Masuo & A. P. Somlyo. (1991). G Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc. Natl. Acad. Sci. USA, 88(20), 9307-9310. DOI : 10.1073/pnas.88.20.9307
  14. A. Gohla, G. Schultz & S. Offermanns. (2000). Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction. Circ. Res, 87(3), 221-227. DOI : 10.1161/01.res.87.3.221
  15. T. Leung et al. (1995). A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J. Biol. Chem, 270(49), 29051-29054. DOI: 10.1074/jbc.270.49.29051
  16. T. Matsui et al. (1996). Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO. J, 15(9), 2208-2216. https://doi.org/10.1002/j.1460-2075.1996.tb00574.x