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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Mar 1;90(5):2087–2091. doi: 10.1073/pnas.90.5.2087

Amplification of nitric oxide signaling by interstitial cells isolated from canine colon.

N G Publicover 1, E M Hammond 1, K M Sanders 1
PMCID: PMC46026  PMID: 8446634

Abstract

The effects of nitric oxide (NO) on intracellular Ca2+ concentration ([Ca2+]i) were studied in enzymatically dispersed interstitial cells (ICs) and smooth muscle cells (SMCs) isolated from canine colon. [Ca2+]i was monitored by using fluo-3 and video fluorescence imaging techniques. Exogenous NO caused an increase in [Ca2+]i in ICs and a decrease in [Ca2+]i in SMCs. Effects of NO on ICs were not blocked by removal of extracellular Ca2+ but were blocked by ryanodine, suggesting that NO caused release of Ca2+ from intracellular stores. When [Ca2+]i was elevated in an IC by micropressure ejection of Bay K 8644, [Ca2+]i decreased in nearby SMCs, suggesting release of a diffusible substance. The diffusible substance may be NO or an NO-related substance based on blockade of transmission by NG-nitro-L-arginine methyl ester, NG-monomethyl-L-arginine, or oxyhemoglobin. The elevation of [Ca2+]i in ICs by NO, which, in turn, might cause further release of NO and elevation of [Ca2+]i, suggests a positive feedback and amplification mechanism in these cells. Elevation of [Ca2+]i in SMCs had no effect on adjacent SMCs. Our data suggest that ICs may play a central role in amplification of NO signaling and propagation of inhibitory wave fronts.

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Selected References

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  1. Berezin I., Huizinga J. D., Daniel E. E. Interstitial cells of Cajal in the canine colon: a special communication network at the inner border of the circular muscle. J Comp Neurol. 1988 Jul 1;273(1):42–51. doi: 10.1002/cne.902730105. [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. Boeckxstaens G. E., Pelckmans P. A., Ruytjens I. F., Bult H., De Man J. G., Herman A. G., Van Maercke Y. M. Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction. Br J Pharmacol. 1991 May;103(1):1085–1091. doi: 10.1111/j.1476-5381.1991.tb12304.x. [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. Conklin J. L., Du C. Guanylate cyclase inhibitors: effect on inhibitory junction potentials in esophageal smooth muscle. Am J Physiol. 1992 Jul;263(1 Pt 1):G87–G90. doi: 10.1152/ajpgi.1992.263.1.G87. [DOI] [PubMed] [Google Scholar]
  7. Dalziel H. H., Thornbury K. D., Ward S. M., Sanders K. M. Involvement of nitric oxide synthetic pathway in inhibitory junction potentials in canine proximal colon. Am J Physiol. 1991 May;260(5 Pt 1):G789–G792. doi: 10.1152/ajpgi.1991.260.5.G789. [DOI] [PubMed] [Google Scholar]
  8. Daniel E. E., Posey-Daniel V. Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal. Am J Physiol. 1984 Mar;246(3 Pt 1):G305–G315. doi: 10.1152/ajpgi.1984.246.3.G305. [DOI] [PubMed] [Google Scholar]
  9. Faussone-Pellegrini M. S., Pantalone D., Cortesini C. Smooth muscle cells, interstitial cells of Cajal and myenteric plexus interrelationships in the human colon. Acta Anat (Basel) 1990;139(1):31–44. doi: 10.1159/000146975. [DOI] [PubMed] [Google Scholar]
  10. Garg U. C., Hassid A. Nitric oxide decreases cytosolic free calcium in Balb/c 3T3 fibroblasts by a cyclic GMP-independent mechanism. J Biol Chem. 1991 Jan 5;266(1):9–12. [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. Imaizumi M., Hama K. An electron microscopic study on the interstitial cells of the gizzard in the love-bird (Uroloncha domestica). Z Zellforsch Mikrosk Anat. 1969;97(3):351–357. doi: 10.1007/BF00968841. [DOI] [PubMed] [Google Scholar]
  13. Langton P., Ward S. M., Carl A., Norell M. A., Sanders K. M. Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7280–7284. doi: 10.1073/pnas.86.18.7280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee H. K., Sanders K. M. Comparison of ionic currents from interstitial cells and smooth muscle cells of canine colon. J Physiol. 1993 Jan;460:135–152. doi: 10.1113/jphysiol.1993.sp019463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Lincoln T. M., Cornwell T. L. Towards an understanding of the mechanism of action of cyclic AMP and cyclic GMP in smooth muscle relaxation. Blood Vessels. 1991;28(1-3):129–137. doi: 10.1159/000158852. [DOI] [PubMed] [Google Scholar]
  17. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  18. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  19. Publicover N. G., Horowitz N. N., Sanders K. M. Calcium oscillations in freshly dispersed and cultured interstitial cells from canine colon. Am J Physiol. 1992 Mar;262(3 Pt 1):C589–C597. doi: 10.1152/ajpcell.1992.262.3.C589. [DOI] [PubMed] [Google Scholar]
  20. Sanders K. M., Ward S. M. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol. 1992 Mar;262(3 Pt 1):G379–G392. doi: 10.1152/ajpgi.1992.262.3.G379. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Suzuki N., Prosser C. L., Dahms V. Boundary cells between longitudinal and circular layers: essential for electrical slow waves in cat intestine. Am J Physiol. 1986 Mar;250(3 Pt 1):G287–G294. doi: 10.1152/ajpgi.1986.250.3.G287. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Thuneberg L. Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol. 1982;71:1–130. [PubMed] [Google Scholar]
  25. Toda N., Baba H., Okamura T. Role of nitric oxide in non-adrenergic, non-cholinergic nerve-mediated relaxation in dog duodenal longitudinal muscle strips. Jpn J Pharmacol. 1990 Jun;53(2):281–284. doi: 10.1254/jjp.53.281. [DOI] [PubMed] [Google Scholar]
  26. Ward S. M., Dalziel H. H., Thornbury K. D., Westfall D. P., Sanders K. M. Nonadrenergic, noncholinergic inhibition and rebound excitation in canine colon depend on nitric oxide. Am J Physiol. 1992 Feb;262(2 Pt 1):G237–G243. doi: 10.1152/ajpgi.1992.262.2.G237. [DOI] [PubMed] [Google Scholar]
  27. Ward S. M., Sanders K. M. Pacemaker activity in septal structures of canine colonic circular muscle. Am J Physiol. 1990 Aug;259(2 Pt 1):G264–G273. doi: 10.1152/ajpgi.1990.259.2.G264. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. 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]

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