Calcitonin Gene-related Peptide Suppresses Pacemaker Currents by Nitric Oxide/cGMP-dependent Activation of ATP-sensitive K+ Channels in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine

  • Choi, Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Parajuli, Shankar Prasad (Department of Physiology, College of Medicine, Chosun University) ;
  • Yeum, Cheol Ho (Department of Physiology, 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) ;
  • Kim, Young Dae (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Cha, Kyoung Hun (Department of Pediatrics, College of Medicine, Chosun University) ;
  • Park, Young Bong (Department of Pediatrics, College of Medicine, Chosun University) ;
  • Park, Jong Seong (Department of Physiology Chonnam National University Medical School) ;
  • Jeong, Han Seong (Department of Physiology Chonnam National University Medical School) ;
  • Jun, Jae Yeoul (Department of Physiology, College of Medicine, Chosun University)
  • 투고 : 2008.01.23
  • 심사 : 2008.04.03
  • 발행 : 2008.08.31

초록

The effects of calcitonin gene-related peptide (CGRP) on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine were investigated using the whole-cell patch clamp technique at $30^{\circ}C$. Under voltage clamping at a holding potential of -70 mV, CGRP decreased the amplitude and frequency of pacemaker currents and activated outward resting currents. These effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor and glibenclamide, a specific ATP-sensitive $K^+$ channels blocker. During current clamping, CGRP hyperpolarized the membrane and this effect was antagonized by glibenclamide. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or naproxen (a cyclooxygenase inhibitor) did not block the CGRP-induced effects, whereas pretreatment with ODQ (a guanylate cyclase inhibitor) or L-NAME (an inhibitor of nitric oxide synthase) did. In conclusion, CGRP inhibits pacemaker currents in ICC by generating nitric oxide via G-protein activation and so activating ATP-sensitive $K^+$ channels. Nitric oxide- and guanylate cyclase-dependent pathways are involved in these effects.

키워드

과제정보

연구 과제 주관 기관 : Chosun University

참고문헌

  1. Bartho, L., Lembeck, F., and Holzer, P. (1987). CGRP is a potent relaxant of intestinal muscle. Eur. J. Pharmacol. 135, 449-51. https://doi.org/10.1016/0014-2999(87)90699-6
  2. Boyer, J.C., Christen, M.O., Balmes, J.L., and Bali, J.P. (1998). Calcitonin gene-related peptide-induced relaxation of isolated human colonic smooth muscle cells through different intracellular pathways. Biochem. Pharmacol. 56, 1097-1104. https://doi.org/10.1016/S0006-2952(98)00130-0
  3. Bulbring, E., and Tomita, T. (1987). Catecholamine action on smooth muscle. Pharmacol. Rev. 39, 49-96.
  4. Burns, A.J., Lomax, A.E.J., Torihashi, S., Sanders, K.M., and Ward, S.M. (1996). Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc. Natl. Acad. Sci. USA 93, 12008-12013.
  5. Choi, S., Chang, I.Y., Yeum, C.H., You, H.J., Park, J.S., Jeong, H.S., So, I., Kim, K.W., and Jun, J.Y. (2006). Activating of ATPdependent $K^+$ channels comprised of Kir 6.2 and SUR2B by $PGE_2$ through $EP_2$ receptor in cultured interstitial cells of Cajal from murine small intestine. Cell. Physiol. Biochem. 18, 187-198. https://doi.org/10.1159/000097516
  6. Grider, J.R., Foxx-Orenstein, A.E., and Jin, J.G. (1998). 5- hydroxytrptamine4 receptor agonist initiates the peristaltic reflex in human, rat, and guinea pig intestine. Gastroenterdogy 115, 370- 380. https://doi.org/10.1016/S0016-5085(98)70203-3
  7. Holzer, P. (1994). Calcitonin gene-related peptide. In Gut Peptides, Biochemistry and Physiology, J.H. Walsh and G.J. Dockray, eds. (New York, USA: Raven Press), pp. 493-523.
  8. Holzer, P. (1998). Implications of tachykinin and calcitonin generelated peptide in inflammatory bowel disease. Digestion 59, 269-283. https://doi.org/10.1159/000007504
  9. Huizinga, J.D., Thuneberg, L., Kluppel, M., Malysz, J., Mikkelsen, H.B., and Bernstein, A. (1995). W/kit gene required for interstitial cells of Cajal for intestinal pacemake activity. Nature 373, 347-349. https://doi.org/10.1038/373347a0
  10. Jun, J.Y., Kong, I.D., Koh, S.D., Wang, X.U., Perrino, B.A., Ward, S.M., and Sanders, K.M. (2001). Regulation of ATP-sensitive $K^+$ channels by protein kinase C in murine colonic myocytes. Am. J. Physiol. 281, C857-C864. https://doi.org/10.1152/ajpcell.2001.281.3.C857
  11. Jun, J.Y., Choi, S., Yeum, C.H., Chang, I.Y., Park, C.K., Kim, M.Y., Kong, I.D., So, I., Kim, K.W., and You, H.J. (2004). Noradrenaline inhibits pacemaker currents through stimulation of $\beta1$- adrenoceptors in cultured interstitial cells of Cajal from murine small intestine. Br. J. Pharmacol. 141, 670-677. https://doi.org/10.1038/sj.bjp.0705665
  12. Jun, J.Y., Choi, S., Chang, I.Y., Yoon, C.K., Jeong, H.G., Kong, I.D., So, I., Kim, K.W., and You, H.J. (2005). Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent $K^+$ channels through prostaglandin $E_2$ in interstitial cells of Cajal from the murine small intestine. Br. J. Pharmacol. 144, 242-251. https://doi.org/10.1038/sj.bjp.0706074
  13. Katsoulis, S., and Conlon, J.M. (1989). CGRPs relax guinea-pig and rat gastric smooth muscle. Eur. J. Pharmacol. 161, 129-134.
  14. Kim, B.J., Jeon, J.H., Kim, S.J., So, I., and Kim, K.W. (2007). Regulation of transient receptor potential melastatin 7 (TRPM7) currents by mitochondria. Mol. Cells 23, 363-369.
  15. Lino, S., and Horiguchi, K. (2006). Interstitial cells of Cajal are involved in neurotransmission in the gastrointestinal tract. Acta Histochem. Cytochem. 39, 145-153. https://doi.org/10.1267/ahc.06023
  16. Maggi, C.A., Giuliani, S., and Zagorodnyuk, V. (1996). Calcitonin gene-related peptide (CGRP) in the circular muscle of guineapig colon: role as inhibitory transmitter and mechanisms of relaxation. Regul. Pept. 61, 27-36. https://doi.org/10.1016/0167-0115(95)00133-6
  17. Murthy, K.S., and Makhlouf, G.M. (1994). Vasoactive intestinal polypeptide/ pituitary adenlate cyclase-activating peptide-dependent activatin of membrane-bound NO synthase in smooth muscle mediated by pertussis toxin-sensitive Gi1-2. J. Biol. Chem. 269, 15977-15980.
  18. Park, C.K., Kim, M.Y., Kim, J.S., Choi, S., Yeum, C.H., Parajuli, S.P., Park, J.S., Jeong, H.S., So, I., Kim, K.W., et al. (2007). Inhibition of pacemaker currents by nitric oxide via activation of ATPsensitive $K^+$ channels in cultured interstitial cells of Cajal from mouse small intestine. Naunyn-Schmiedeberg Arch. Pharmacol. 376, 175-184. https://doi.org/10.1007/s00210-007-0187-1
  19. Publicover, N.G., Hammond, E.M., and Sanders, K.M. (1993). Amplification of nitric oxide signaling by interstitial cells isolated from canine colon. Proc. Natl. Acad. Sci. USA 90, 2087-2091.
  20. Quayle, J.M., Bonev, A.D., Brayden, J.E., and Nelson, M.T. (1994). Calcitonin gene-related peptide activated ATP-sensitive $K^+$ currents in rabbit arterial smooth muscle via protein kinase A. J. Physiol. 475, 9-13. https://doi.org/10.1113/jphysiol.1994.sp020045
  21. Quayle, J.M., Bonev, A.D., Brayden, J.E., and Nelson, M.T. (1997). ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol. Rev. 77, 1165-1232. https://doi.org/10.1152/physrev.1997.77.4.1165
  22. Randall, M.D., and Mculloch, A.I. (1995). The involvement of ATPsensitive potassium channels in $\beta$-adrenoceptor-mediated vasorelaxation in the rat isolated mesenteric arterial bed. Br. J. Pharmacol. 115, 607-612. https://doi.org/10.1111/j.1476-5381.1995.tb14975.x
  23. Rasmussen, T.N., Schmidt, P., Poulsen, S.S., and Holst, J.J. (2001). Localisation and neural control of the release of calcitonin generelated peptide (CGRP) from isolated perfused porcine ileum. Regul. Pept. 98, 137-143. https://doi.org/10.1016/S0167-0115(00)00242-1
  24. Rekik, M., Delvaux, M., Frexinos, J., and Bueno, L. (1997). The calcitonin gene-related peptide activates both cAMP and NO pathways to induce relaxation of circular smooth muscle cells of guinea-pig ileum. Peptides 18, 1517-1522. https://doi.org/10.1016/S0196-9781(97)00246-5
  25. Sanders, K.M. (1998). G protein-coupled receptors in gastrointestinal physiology IV. Neural regulation of gastrointestinal smooth muscle. Am. J. Physiol. 275, G1-G7. https://doi.org/10.1152/ajpcell.1998.275.3.Ca1
  26. Sanders, K.M. (2006). Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu. Rev. Physiol. 68, 307-343. https://doi.org/10.1146/annurev.physiol.68.040504.094718
  27. Terzic, A., Tung, R.T., Inanobe, A., Katada, T., and Kurachi, Y. (1994). G proteins activate ATP-sensitive $K^+$ channels by antagonizing ATP-dependent gating. Neuron 12, 885-893. https://doi.org/10.1016/0896-6273(94)90340-9
  28. Ward, S.M., and Sanders, K.M. (2006). Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract. J. Physiol. 576, 675-682. https://doi.org/10.1113/jphysiol.2006.117390
  29. Ward, S.M., Burns, A.J., Torihashi, S., and Sanders, K.M. (1994). Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J. Physiol. 480, 91-97. https://doi.org/10.1113/jphysiol.1994.sp020343
  30. Ward, S.M., Beckett, E.A., Wang, X., Baker, F., Khoyi, M., and Sanders, K.M. (2000). Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric neurons. J. Neurosci. 20, 1393-1403. https://doi.org/10.1523/JNEUROSCI.20-04-01393.2000
  31. Zhang, L., Bonev, A.D., Nelson, M.T., and Mawe, G.M. (1994a). Activation of ATP-sensitive potassium currents in guinea-pig gall-bladder smooth muscle by neuropeptide CGRP. J. Physiol. 478, 483-491. https://doi.org/10.1113/jphysiol.1994.sp020267
  32. Zhang, L., Bonev, A.D., Mawe, G.M., and Nelson, M.T. (1994b). Protein kinase A mediates activation of ATP-sensitive $K^+$ currents by CGRP in gallbladder smooth muscle. Am. J. Physiol. 267, G494-G499.