Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 Mar 15;499(Pt 3):773–786. doi: 10.1113/jphysiol.1997.sp021968

Basal release of nitric oxide induces an oscillatory motor pattern in canine colon.

K D Keef 1, D C Murray 1, K M Sanders 1, T K Smith 1
PMCID: PMC1159294  PMID: 9130172

Abstract

1. The consequences of intrinsic, basal nitric oxide release on electrical and contractile activity of canine proximal colon were examined. Membrane potential and contraction were simultaneously recorded from the circular muscle in the presence of drugs to block adrenergic and cholinergic responses. 2. Electrical slow waves were recorded from muscle cells near the submucosal surface of the circular layer. Spontaneous contractions were initiated by each slow wave. Contractile amplitude increased 1.9-fold when nerves were blocked with tetrodotoxin (TTX, 1 microM). 3. Muscle cells near the myenteric surface displayed myenteric potential oscillations (MPOs) averaging 16 cycles per minute (c.p.m.) in frequency and 10 mV in amplitude. Twenty-five per cent of muscles displayed an additional slow, neurogenic oscillation (mean frequency, 1 c.p.m.; amplitude, 14 mV) superimposed upon the MPO rhythm. 4. The nitric oxide (NO) synthase inhibitor N omega -nitro-L-arginine (L-NA, 100 microM; n = 16) abolished neurogenic oscillations, depolarized cells, and increased MPO upstroke velocity, amplitude and frequency. The actions of L-NA were mimicked by N omega-nitro-L-arginine methylester (L-NAME, 100 microM) and oxyhaemoglobin (3%). 5. Spontaneous contractions were increased 2.3-fold by L-NA, and TTX had no effect on contractions after addition of L-NA. 6. The NO-donor sodium nitroprusside (SNP, 1 microM) reversed the electrical and mechanical effects of L-NA and initiated slow oscillations similar to the neurogenic oscillations. Slow oscillations were also evoked with S-nitroso-N-acetylpenicillamine (SNAP, 1 microM). The effects of NO donors were blocked by oxyhaemoglobin. 7. Slow electrical oscillations could not be elicited by SNP after removal of a thin strip of circular muscle along the myenteric edge. 8. These data suggest that the spontaneous electrical and contractile activity of the proximal colon is tonically suppressed by basal release of NO. Basal NO causes an oscillatory pattern of electrical and mechanical activity. This activity does not require patterned firing of nerves; rather a continuous, low level release of NO would be capable of producing the neurogenic oscillatory behaviour. The slow oscillatory activity depends upon the presence of the myenteric region of the circular muscle layer, which contains cell bodies of enteric neurons and interstitial cells of Cajal.

Full text

PDF
773

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belai A., Schmidt H. H., Hoyle C. H., Hassall C. J., Saffrey M. J., Moss J., Förstermann U., Murad F., Burnstock G. Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut. Neurosci Lett. 1992 Aug 31;143(1-2):60–64. doi: 10.1016/0304-3940(92)90233-w. [DOI] [PubMed] [Google Scholar]
  2. Boeckxstaens G. E., Pelckmans P. A., Bult H., De Man J. G., Herman A. G., Van Maercke Y. M. Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol. 1990 Nov 6;190(1-2):239–246. doi: 10.1016/0014-2999(90)94132-h. [DOI] [PubMed] [Google Scholar]
  3. Bowman A., Gillespie J. S. Block of some non-adrenergic inhibitory responses of smooth muscle by a substance from haemolysed erythrocytes. J Physiol. 1982 Jul;328:11–25. doi: 10.1113/jphysiol.1982.sp014250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  5. Bult H., Boeckxstaens G. E., Pelckmans P. A., Jordaens F. H., Van Maercke Y. M., Herman A. G. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990 May 24;345(6273):346–347. doi: 10.1038/345346a0. [DOI] [PubMed] [Google Scholar]
  6. Burns A. J., Lomax A. E., Torihashi S., Sanders K. M., Ward S. M. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12008–12013. doi: 10.1073/pnas.93.21.12008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clapp L. H., Gurney A. M. Modulation of calcium movements by nitroprusside in isolated vascular smooth muscle cells. Pflugers Arch. 1991 Jun;418(5):462–470. doi: 10.1007/BF00497774. [DOI] [PubMed] [Google Scholar]
  8. Du C., Carl A., Smith T. K., Sanders K. M., Keef K. D. Mechanism of cyclic AMP-induced hyperpolarization in canine colon. J Pharmacol Exp Ther. 1994 Jan;268(1):208–215. [PubMed] [Google Scholar]
  9. Furness J. B., Costa M. The participation of enteric inhibitory nerves in accommodation of the intestine to distension. Clin Exp Pharmacol Physiol. 1977 Jan-Feb;4(1):37–41. doi: 10.1111/j.1440-1681.1977.tb02375.x. [DOI] [PubMed] [Google Scholar]
  10. Gillespie J. S., Liu X. R., Martin W. The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol. 1989 Dec;98(4):1080–1082. doi: 10.1111/j.1476-5381.1989.tb12650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grider J. R., Murthy K. S., Jin J. G., Makhlouf G. M. Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol. 1992 Apr;262(4 Pt 1):G774–G778. doi: 10.1152/ajpgi.1992.262.4.G774. [DOI] [PubMed] [Google Scholar]
  12. Huizinga J. D., Chang G., Diamant N. E., El-Sharkawy T. Y. Electrophysiological basis of excitation of canine colonic circular muscle by cholinergic agents and substance P. J Pharmacol Exp Ther. 1984 Dec;231(3):692–699. [PubMed] [Google Scholar]
  13. Ishikawa T., Hume J. R., Keef K. D. Regulation of Ca2+ channels by cAMP and cGMP in vascular smooth muscle cells. Circ Res. 1993 Dec;73(6):1128–1137. doi: 10.1161/01.res.73.6.1128. [DOI] [PubMed] [Google Scholar]
  14. Keef K. D., Du C., Ward S. M., McGregor B., Sanders K. M. Enteric inhibitory neural regulation of human colonic circular muscle: role of nitric oxide. Gastroenterology. 1993 Oct;105(4):1009–1016. doi: 10.1016/0016-5085(93)90943-7. [DOI] [PubMed] [Google Scholar]
  15. Keef K. D., Ward S. M., Stevens R. J., Frey B. W., Sanders K. M. Electrical and mechanical effects of acetylcholine and substance P in subregions of canine colon. Am J Physiol. 1992 Feb;262(2 Pt 1):G298–G307. doi: 10.1152/ajpgi.1992.262.2.G298. [DOI] [PubMed] [Google Scholar]
  16. Koh S. D., Campbell J. D., Carl A., Sanders K. M. Nitric oxide activates multiple potassium channels in canine colonic smooth muscle. J Physiol. 1995 Dec 15;489(Pt 3):735–743. doi: 10.1113/jphysiol.1995.sp021087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koh S. D., Sanders K. M. Modulation of Ca2+ current in canine colonic myocytes by cyclic nucleotide-dependent mechanisms. Am J Physiol. 1996 Sep;271(3 Pt 1):C794–C803. doi: 10.1152/ajpcell.1996.271.3.C794. [DOI] [PubMed] [Google Scholar]
  18. Li C. G., Rand M. J. Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 1989 Dec;16(12):933–938. doi: 10.1111/j.1440-1681.1989.tb02404.x. [DOI] [PubMed] [Google Scholar]
  19. Liu L. W., Huizinga J. D. Electrical coupling of circular muscle to longitudinal muscle and interstitial cells of Cajal in canine colon. J Physiol. 1993 Oct;470:445–461. doi: 10.1113/jphysiol.1993.sp019868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lyster D. J., Bywater R. A., Taylor G. S. Neurogenic control of myoelectric complexes in the mouse isolated colon. Gastroenterology. 1995 May;108(5):1371–1378. doi: 10.1016/0016-5085(95)90684-3. [DOI] [PubMed] [Google Scholar]
  21. Ozaki H., Blondfield D. P., Hori M., Publicover N. G., Kato I., Sanders K. M. Spontaneous release of nitric oxide inhibits electrical, Ca2+ and mechanical transients in canine gastric smooth muscle. J Physiol. 1992 Jan;445:231–247. doi: 10.1113/jphysiol.1992.sp018921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pollock J. S., Nakane M., Buttery L. D., Martinez A., Springall D., Polak J. M., Förstermann U., Murad F. Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies. Am J Physiol. 1993 Nov;265(5 Pt 1):C1379–C1387. doi: 10.1152/ajpcell.1993.265.5.C1379. [DOI] [PubMed] [Google Scholar]
  23. Publicover N. G., Hammond E. M., Sanders K. M. Amplification of nitric oxide signaling by interstitial cells isolated from canine colon. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2087–2091. doi: 10.1073/pnas.90.5.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanders K. M., Smith T. K. Enteric neural regulation of slow waves in circular muscle of the canine proximal colon. J Physiol. 1986 Aug;377:297–313. doi: 10.1113/jphysiol.1986.sp016188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smith T. K., Reed J. B., Sanders K. M. Electrical pacemakers of canine proximal colon are functionally innervated by inhibitory motor neurons. Am J Physiol. 1989 Mar;256(3 Pt 1):C466–C477. doi: 10.1152/ajpcell.1989.256.3.C466. [DOI] [PubMed] [Google Scholar]
  26. Smith T. K., Reed J. B., Sanders K. M. Interaction of two electrical pacemakers in muscularis of canine proximal colon. Am J Physiol. 1987 Mar;252(3 Pt 1):C290–C299. doi: 10.1152/ajpcell.1987.252.3.C290. [DOI] [PubMed] [Google Scholar]
  27. Smith T. K., Reed J. B., Sanders K. M. Origin and propagation of electrical slow waves in circular muscle of canine proximal colon. Am J Physiol. 1987 Feb;252(2 Pt 1):C215–C224. doi: 10.1152/ajpcell.1987.252.2.C215. [DOI] [PubMed] [Google Scholar]
  28. Stark M. E., Bauer A. J., Szurszewski J. H. Effect of nitric oxide on circular muscle of the canine small intestine. J Physiol. 1991 Dec;444:743–761. doi: 10.1113/jphysiol.1991.sp018904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thornbury K. D., Ward S. M., Dalziel H. H., Carl A., Westfall D. P., Sanders K. M. Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon. Am J Physiol. 1991 Sep;261(3 Pt 1):G553–G557. doi: 10.1152/ajpgi.1991.261.3.G553. [DOI] [PubMed] [Google Scholar]
  30. Torihashi S., Horowitz B., Pollock J. S., Ward S. M., Xue C., Kobayashi S., Sanders K. M. Expression of nitric oxide synthase in mucosal cells of the canine colon. Histochem Cell Biol. 1996 Jan;105(1):33–41. doi: 10.1007/BF01450876. [DOI] [PubMed] [Google Scholar]
  31. Ward S. M., Dalziel H. H., Bradley M. E., Buxton I. L., Keef K., Westfall D. P., Sanders K. M. Involvement of cyclic GMP in non-adrenergic, non-cholinergic inhibitory neurotransmission in dog proximal colon. Br J Pharmacol. 1992 Dec;107(4):1075–1082. doi: 10.1111/j.1476-5381.1992.tb13409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ward S. M., Xue C., Shuttleworth C. W., Bredt D. S., Snyder S. H., Sanders K. M. NADPH diaphorase and nitric oxide synthase colocalization in enteric neurons of canine proximal colon. Am J Physiol. 1992 Aug;263(2 Pt 1):G277–G284. doi: 10.1152/ajpgi.1992.263.2.G277. [DOI] [PubMed] [Google Scholar]
  33. Wood J. D. Excitation of intestinal muscle by atropine, tetrodotoxin, and xylocaine. Am J Physiol. 1972 Jan;222(1):118–125. doi: 10.1152/ajplegacy.1972.222.1.118. [DOI] [PubMed] [Google Scholar]
  34. Xie Q. W., Cho H. J., Calaycay J., Mumford R. A., Swiderek K. M., Lee T. D., Ding A., Troso T., Nathan C. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science. 1992 Apr 10;256(5054):225–228. doi: 10.1126/science.1373522. [DOI] [PubMed] [Google Scholar]
  35. Xue C., Pollock J., Schmidt H. H., Ward S. M., Sanders K. M. Expression of nitric oxide synthase immunoreactivity by interstitial cells of the canine proximal colon. J Auton Nerv Syst. 1994 Sep;49(1):1–14. doi: 10.1016/0165-1838(94)90015-9. [DOI] [PubMed] [Google Scholar]
  36. Young H. M., Furness J. B., Shuttleworth C. W., Bredt D. S., Snyder S. H. Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine. Histochemistry. 1992 May;97(4):375–378. doi: 10.1007/BF00270041. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES