The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지

Involvement of Thromboxane $A_2$ in the Modulation of Pacemaker Activity of Interstitial Cells of Cajal of Mouse Intestine

  • Kim, Jin-Ho (Departments of Neurology, College of Medicine, Chosun University) ;
  • Choe, Soo-Jin (Department of Radiology, Gacheon University Gil Medical Center) ;
  • Yeum, Cheol-Ho (Departments of Physiology, College of Medicine, Chosun University) ;
  • Yoon, Pyung-Jin (Departments of Physiology, College of Medicine, Chosun University) ;
  • Choi, Seok (Departments of Physiology, College of Medicine, Chosun University) ;
  • Jun, Jae-Yeoul (Departments of Physiology, College of Medicine, Chosun University)
  • Published : 2008.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Although many studies show that thromboxane $A_2\;(TXA_2)$ has the action of gastrointestinal (GI) motility using GI muscle cells and tissue, there are no reports on the effects of $TXA_2$ on interstitial cells of Cajal (ICC) that function as pacemaker cells in GI tract. So, we studied the modulation of pacemaker activities by $TXA_2$ in ICC with whole cell patch-clamp technique. Externally applied $TXA_2\;(5{\mu}M)$ produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode. The tonic inward currents by $TXA_2$ were inhibited by intracellular application of GDP-${\beta}$-S. The pretreatment of ICC with $Ca^{2+}$ free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the $TXA_2$-induced tonic inward currents. However, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the $TXA_2$-induced effects on pacemaker currents. These results suggest that $TXA_2$ can regulate intestinal motility through the modulation of ICC pacemaker activities. This modulation of pacemaker activities by $TXA_2$ may occur by the activation of G protein and PKC independent pathway via extra and intracellular $Ca^{2+}$ modulation.

Keywords

References

  1. Arita H, Nakano T, Hanasaki K. Thromboxane $A_2$: its generation and role in platelet activation. Prog Lipid Res 28: 273-301, 1989 https://doi.org/10.1016/0163-7827(89)90002-7
  2. Bennett A, Elev KG, Scholes GB. Effects of prostaglandins $E_1$ and $E_2$ on human, guinea pig and rat isolated small intestine. Br J Pharmacol 34: 630-638, 1968 https://doi.org/10.1111/j.1476-5381.1968.tb08492.x
  3. Bennett A, Hensy CN, Sanger GJ, Stamford IF. Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers. Br J Pharmacol 74: 435-444, 1981 https://doi.org/10.1111/j.1476-5381.1981.tb09989.x
  4. Bennett A, Sanger GJ. Pinane thromboxane $A_2$ analogues are non-selective prostanoid antagonists in rat and human stomach muscle. Br J Pharmacol 77: 591-596, 1982 https://doi.org/10.1111/j.1476-5381.1982.tb09336.x
  5. Berezin I, Daniel EE, Huizinga JD. Ultrastructure of interstitial cells of Cajal in the canine distal esophagus. Can J Physiol Pharmacol 72: 1049-1059, 1994 https://doi.org/10.1139/y94-147
  6. Berezin I, Huizinga JD, Daniel EE. Interstitial cells of Cajal in the canine colon: a special communication network at the inner border of the circular muscle. J Comp Neurol 273: 42-51, 1988 https://doi.org/10.1002/cne.902730105
  7. Brass LF, Shaller CC, Belmonte EJ. Inositol 1,4,5-triphosphate induced granule secretion in platelets, Evidende that the activation of phospholipase C mediated by platelet thromboxane receptors involves a guanine nucleotide binding protein-dependent mechanism distinct from that of thrombin. J Clin Invest 79: 1269-1275, 1987 https://doi.org/10.1172/JCI112947
  8. Coleman RA, Humphrey PP, Kennedy I, Levy GP, Lumley P. Comparison of the actions of U-46619, a prostaglandin $H_2$-analogue, with those of prostaglandin $H_2$ and thromboxane $A_2$ on some isolated smooth muscle preparations. Br J Pharmacol 73: 773-778, 1981 https://doi.org/10.1111/j.1476-5381.1981.tb16814.x
  9. Daniel EE, Posey-Daniel V. Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal. Am J Physiol 246: G305-G315, 1984
  10. Ferreira SH, Herman AG, Vane JR. Prostaglandin production by rabbit isolated jejunum and its relationship to the inherent tone of the preparation. Br J Pharmacol 56: 469-477, 1976 https://doi.org/10.1111/j.1476-5381.1976.tb07459.x
  11. Koh SD, Sanders KM, Ward SM. Spontaneous electrical rhythmicity in cultured interstitial cells of Cajal from the mouse small intestine. J Physiol 513: 203-213, 1998 https://doi.org/10.1111/j.1469-7793.1998.203by.x
  12. LeDuc LE, Needleman P. Regional localization of prostacyclin and thromboxane synthesis in dog stomach and intestinal tract. J Pharmacol Exp Ther 211: 181-188, 1979
  13. Nakano T, Hanasaki K, Arita H. Different effects of two thromboxane $A_2$/prostaglandin $H_2$ receptor ligand, U46619 and S-14, on rabbit platelets. FEBS Lett 234: 309-312, 1988 https://doi.org/10.1016/0014-5793(88)80105-4
  14. Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB. Arachidonic acid metabolism. Annu Rev Biochem 55: 69-109, 1986 https://doi.org/10.1146/annurev.bi.55.070186.000441
  15. Okada Y, Hara A, Ma H, Xiao CY, Takahata O, Kohgo Y, Narumiya S, Ushikubi F. Characterization of prostanoid receptors mediating contraction of the gastric fundus and ileum: studies using mice deficient in prostanoid receptors. Br J Pharmacol 131: 745-755, 2000 https://doi.org/10.1038/sj.bjp.0703627
  16. Pollock WK, Armstrong RA, Brydon LJ, Jones RL, Macintyre DE. Thromboxane-induced phosphatide formation in human platelets. Relationship to receptor occupancy and to changes in cytosolic free calcium. Biochem J 219: 833-842, 1984 https://doi.org/10.1042/bj2190833
  17. Portbury AL, Furness JB, Young HM, Southwell BR, Vigna SR. Localization of NK1 receptor immunoreactivity to neurons and interstitial cells of the guinea-pig gastrointestinal tract. J Comp Neurol 367: 342-351, 1996 https://doi.org/10.1002/(SICI)1096-9861(19960408)367:3<342::AID-CNE2>3.0.CO;2-5
  18. Publicover NG, Horowitz NN, Sanders KM. Calcium oscillations in freshly dispersed and cultured interstitial cells of from canine colon. Am J Physiol 262: C589-C597, 1992 https://doi.org/10.1152/ajpcell.1992.262.3.C589
  19. Robert A. Prostaglandins and the gastrointestinal tract. In: Hohnson LR ed, Physiology of the Gastrointestinal Tract. 1st ed. Raven, New York, p 1407-1434, 1981
  20. Sage SO, Rink TJ. The kinetics of changes in intracellular calcium concentration in fura-2-loaded human platelets. J Biol Chem 262: 16364-16369, 1987
  21. Sanders KM. Evidence that endogenous prostacyclin modulates the electrical and mechanical activities of canine ileal circular muscle. J Gastroenterol 19: 401, 1981
  22. Sanders KM. Evidence that prostaglandins are local regulatory agents in canine ileal circular muscle. Am J Physiol 246: G361-G371, 1984
  23. Sanders KM. Ionic mechanisms of electrical rhythmicity in gastrointestinal smooth muscles. Annu Rev Physiol 54: 439-453, 1992 https://doi.org/10.1146/annurev.ph.54.030192.002255
  24. Shenker A, Goldsmith P, Unson CG, Spiegel AM. The G protein coupled to the thromboxane $A_2$ receptor in human platelets is a member of the novel $G_q$ family. J Biol Chem 266: 9309-9313, 1991
  25. Shuttleworth CWR, Xue C, Ward SM, de Vente J, Sanders KM. Immunohistochemical localization of 3',5'-cyclic guanosine monophosphate in the canine proximal colon: responses to nitric oxide and electrical stimulation of enteric inhibitory neurons. Neuroscience 56: 513-522, 1993 https://doi.org/10.1016/0306-4522(93)90350-O
  26. Siess W, Stifel M, Binder H, Weber PC. Activation of V1-receptors by vasopressin stimulates inositol phospholipids hydrolysis and arachidonate metabolism in human platelets. Biochem J 233: 83-91, 1986 https://doi.org/10.1042/bj2330083
  27. Sternini C, Su D, Gamp PD, Bunnett NW. Cellular sites of expression of the neurokinin-1 receptor in the rat gastrointestinal tract. J Comp Neurol 258: 531-540, 1995
  28. Thomsen L, Robinson TL, Lee JCF, Farraway L, Hughes MJH, Andrews DW, Huizinga JD. Interstitial cells of Cajal generate a rhythmic pacemaker current. Nature Med 4: 448-451, 1998
  29. Thuneberg L. Interstitial cells of Cajal: intestinal pacemakers? Adv Anat Embryol Cell Biol 71: 11-30, 1982
  30. Torihashi S, Kobayashi S, Gerthoffer WT, Sanders KM. Interstitial cells in deep muscular plexus of canine small intestine may be specialized smooth muscle cells. Am J Physiol 265: G638-G645, 1993
  31. Watson SP, Reep B, McConnell RT, Lapetina EG. Collagen stimulates [3H]inositol trisphosphate formaton in indomethacin-treated human platelets. Biochem J 226: 831-837, 1985 https://doi.org/10.1042/bj2260831
  32. Young HM, McConalogue K, Fruness JB, de Vente J. Nitric oxide targets in the guinea-pig intestine identified by induction of cyclic GMP immunoreactivity. Neuroscience 55: 583-596, 1993 https://doi.org/10.1016/0306-4522(93)90526-L
  33. Zhou DS, Komuro T. Interstitial cells associated with the deep muscular plexus of the guinea-pig small intestine, with special reference to the interstitial cells of Cajal. Cell Tissue Res 268: 205-216, 1992 https://doi.org/10.1007/BF00318788