The Relaxant Effect of Nitric Oxide Donor on the Contractile Activity of Ileal: Role of Cgmp and Potassium Channels

  • Omar Abdul Majeed Al-Habib University of Zakho
Keywords: Nitric oxide, Potassium channels, cGMP, Ileal, Organ bath


Nitric oxide (NO) is a small molecule of endogenous gases and has important physiological functions. It is well known that NO is an inhibitory action of gastrointestinal smooth muscle cells. The aim of this study was to determine the role of cyclic guanosine monophosphate (cGMP) and potassium (K+) channels in relaxation induced by NO of ileal smooth muscles. Sodium nitroprusside (SNP) at doses between (1X10-6to 3X10-4 M) showed more potent relaxant effect in acetylcholine (ACh) (10-5M) than potassium chloride (KCl) (60mM) induced ileal smooth muscle contractions. Before precontraction by ACh, the segments of ileum was incubated for (20) minutes with various blockers such as Methylene blue (MB), Glibenclamide (GLIB), 4-aminopyridine (4-AP), Barium Chloride (BaCl2) and Tetraethylammonium (TEA). In the presence of MB (3mM), 4-AP (1mM), BaCl2 (1mM) and TEA (1mM) significantly inhibited SNP induced relaxation, while GLIB (10-5M) was not able to affect the response to SNP. These results suggested that NO play an important role in the relaxation of ileal, and these effects are mediated via cGMP, voltage-dependent (KV), inward rectifier (KIR) and Ca+2-dependent (KCa) channels.


Author Biography

Omar Abdul Majeed Al-Habib, University of Zakho

Dept. of Biology, Faculty of Science, University of Zakho, Kurdistan Region- Iraq.


Agasti, T. K. (2011) Textbook of Anesthesia for Postgraduates. JP Medica Ltd.
Ahern, G.P., Klyachko, V.A. and Jackson, M.B. (2002) cGMP and S- nitrosylation: two routes for modulation of neuronal excitability by NO. Trends Neurosci; 25(10): 510-517
arachidonic acid. J Pharmacol Exp Ther; 237: 893-900
Borrelli, F., Capasso, F., Capasso, R., Ascione, V., Aviello, G., Longo, R., and Izzo, AA. (2006) Effect of Boswellia serrata on intestinal motility in rodents: Inhibition of diarrhoea without constipation. Br. J. Pharmacol.; 148(4): 553-560 .
Chung, SS., Ahn, DS., Lee, HG., Lee, YH. and Nam, TS. (2005) Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes. Exp Physiol; 90(4):577-586
Duncan, C., Dougall, H., Johnston, P. Green, S., Brogan, R., Leifert C, Smith L, Golden M., and Benjamin N. (1995) Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat. Med.;1 (6): 546-551
Estevez, A G. and Jordan J. (2002) Nitric Oxide and Superoxide, a Deadly Cocktail. Ann. N.Y. Acad. Sci; 962: 207-211
Feelisch, M. (2008) The chemical biology of nitric oxide – an outsider’s reflections about its role in osteoarthritis. Osteoarthritis and Cartilage; 16(2):S3-S13
Flatley, J., Barrett, J., Pullan, S T., Hughes, M N.,
Green, J. and Poole, RK. (2005) Transcriptional
responses of Escherichia coli to S- nitrosogluta-
thione under defined chemostat conditions
reveal major changes in methionine biosynthesis.
J Biol Chem.; 280 (11):10065-10072
Grasa, L., Rebollar, E., Arruebo, M.P., Plaza, M.A. and
Murillo, M.D. (2005) The role of NO in the
contractility of rabbit small intestine in vitro:
Effect of K+ channela. Journal of Physiology &
Pharmacology; 56(3):407- 419
Huerta, S., Chilka, S., and Bonavida, B. (2008) Nitric oxide donors: Novel cancer therapeutics (Review). International Journal of Oncology; 33(5):909-927
Ignarro LJ, Harbison RG, Wood KS, and Kadowitz
PJ. (1986) Activation of purified soluble
guanylate cyclase by endothelium - derived
relaxing factor from intrapulmonary artery
and vein: stimulation by acetylcholine
bradykinin and arachidonic acid. J Pharmaco
Exp Ther; 237:893-900
Ijoma, S.C., Challis, R.A., and Boyle, J.P. (1995) Comparative effects of activation of soluble and particulate guanylyl cyclase on cGMP elevation and relaxation of bovine tracheat smooth muscle. Br. J. Pharmacol; 115(5):723-732
Kanada, A., Hata F., Suthamnatpong, N., Maehara, T., Ishii, T. Takeuchi, T. and Yagasaki O. (1992) Key roles of nitric oxide and cyclic GMP in nonadrenergic and noncholinergic inhibition in rat ileum. Eur. J. Pharmacol; 216(2):287-292
Kashiba, M., kajimura, M., Goda, N., and Suematsu, M. (2002) From O2 to H2S a landscape view of gas biology. Keio J Med; 51(1):1-10
Kasparek, M.S., Linden, D.R., kreis, M.E., and Sarr, M.G. (2008) Gasotrasmitters in the gastrointestinal. Surgers; 143(4):455-459
Kaya, T.T., Koyluoglu, G., Soydan, AS., Arpacik, M., and Karadas, B. (2002) Effects of nimesulide and pentoxifylline on decreased contractile responses in rat ileum with peritonitis. Eur. J. Pharmacol.; 442(1-2):147-153
Kishore, D.V. and Rahman, R. (2012) Spasmolytic Activity of Casuarine Equisetifolia Bark Extract. IJPSR; 3(5):1452-1456
Kochar, N I., Chandewal, AV., Bakal R L., and Kochar P N. (2011) Nitric Oxide and the Gastrointestinal Tract. International Journal of Pharmacology; 7(1): 31-39
Koh, S.D., Campbell, J.D., Cari, A. and Sanders, K.M. (1995). Nitric oxide activates multiple potassium channels in canine colonic smooth muscle. J. Physiol., 489, 735-743
Lang, R.J. and Watson, M.J. (1998) Effects of nitric oxide donors, S-nitroso-L- cysteine and sodium nitroprusside, on the whole-cell and single channel currents in single myocytes of the guinea-pig proximal colon. Br. J. Pharmacol.; 123(3): 505-517
Lecci, A., Santicioli, P., and Maggi, C.A. (2002) Pharmacology of transmission to gastrointestinal muscle. Curr Opin Pharmacol ; 2(6):630–641
Liang, C., Luo, H., Liu, Y., Cao, J., and Xia, H. (2012) Plasma Hormones Facilitated the Hypermotility
of the Colon in a Chronic Stress Rat Model. PLoS One; 7(2): e31774
Littleton, J.T., and Ganetzky, B. (2000) "Ion channels and synaptic organization: analysis of the Drosophila genome". Neuron; 26 (1): 35-43
Miller, M.R., and Megson, I.L. (2007) Recent developments in nitric oxide donor drugs. Br J Pharmacol; 151(3):305-321
Moncada, S. and Higgs, A. (1993) The L-arginine-nitric oxide pathway. N Engl J Med, 329(27): 2002-2012
Naseri, MK., Naseri, ZG., Mohammadian, M., and Birgani, MO. (2008) Ileal relaxation induced by Mentha longifolia (L.) leaf extract in rat. Pak J Biol Sci.; 11(12):1594-1599
Patil, C.S., Singh, V.P., Jain, N.K., and Kulkarni, S.K. (2005) Inhibitory effect of sildenafil on gastrointestinal smooth muscle: role of NO-cGMP transduction pathway. Indian J. Exp. Biol.; 43(2): 167-171
Poole, RK. (2008) Methods in Enzymology, Vol.437: Globins and Other Nitric Oxide-Reactive Proteins, Part B. Elsevier Inc.

Ratz, PH., Berg, KM., Urban, NH., and Miner, AS. (2005) Regulation of smooth muscle calcium sensitivity: KCl as a calcium sensitizing stimulus. Am J Physiol Cell Physiol 288(4):C769-C783
Robertson BE., Schubert R., Hescheler J., and Nelson MT. (1993) cGMP-dependent protein kinase activates Caactivated K channels in cerebral artery smooth muscle cells. Am J Physiol; 265: C299-C303
Shen, Z., Yang, Q., and You, Q. (2009) Researches toward potassium channels on tumor progressions. Current Topics Medicinal Chemistry; 9(4):322-329 .
Shieh, CC., S., Coghlan, M., Sullivan J., P., and Gopalakrishnan M. (2000) Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities. Pharmacological Reviews, 52 (4) 557-594
Sperelakis, N. (2001) Sperelakis Cell Biology Sourcebook: A Molecular Approach, 3th edition. Academic Press, USA.
Takahshi, T. (2003) " Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract". J Gastroenterol; 38(5):421-430
Ueno, T., Duenes, J.A., Zarroug, A.E., and Sarr, M.G. (2004) Nitrergic mechanisms mediating inhibitory control of longitudinal smooth muscle contraction in mouse small intestine. J. Gastrointest. Surg.; 8(7): 831-841
Vanneste, G., Robberecht, P., and Lefebvre, R.A., (2004) Inhibitory pathways in the circular muscle of rat jejunum. Br. J. Pharmacol.; 143(1):107-118
Willmot, M.R. and Bath, PM. (2003) "The potential of nitric oxide therapeutics in stroke". Expert Opinion Investigational Drugs; 12(3): 455-470.
Wink, D.A, Vodovotz, Y, Laval, J, Laval F., Dewhirst, M.W., and Mitchell, J.B. (1998) The multifaceted roles of nitric oxide in cancer. Carcinogenesis. 19(5):711-721
Yamamoto, T. and Bing, RJ. (2000) Nitric oxide donors. Proc Soc Exp BiolMed.; 225(3): 200-206
Zhang, W.W., Y. Li, X.Q. Wang,F., Tian, H. Cao, M.W. Wang and Sun, Q.S. (2005) Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement. World J. Gastroenterol.; 11(28): 4414-4418
Zizzo, MG., Mulè, F., and Serio, R. (2005) Mechanisms underlying the nitric oxide inhibitory effects in mouse ileal longitudinal muscle. Can J Physiol Pharmacol. ; 83(8-9):805-810
Zyromski, N.J., Duenes, J.A., Kendrick, M.L., Balsiger, B.M., Farrugia, G., and Sarr, M.G., (2001) Mechanism mediating nitric oxide-induced inhibition in human jejunal longitudinal smooth muscle. Surgery; 130(3): 489-496
How to Cite
Al-Habib, O. (2013). The Relaxant Effect of Nitric Oxide Donor on the Contractile Activity of Ileal: Role of Cgmp and Potassium Channels. Science Journal of University of Zakho, 1(2), 583-590. Retrieved from
Science Journal of University of Zakho