Skip to main content
SpringerLink
Log in

Projections of nitric oxide synthesizing neurons in the guinea-pig colon

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The neuronal form of the enzyme nitric oxide synthase, which is an obligatory constituent of neurons that utilise nitric oxide as a transmitter, was revealed histochemically in this study by its ability to transfer a proton from reduced nicotinamide adenine dinucleotide phosphate to nitro-blue tetrazolium. In the guinea-pig colon, nitric oxide synthase was located in numerous irregularly-shaped myenteric neurons with single axons. In the submucosa, a small number of neurons had strong enzyme activity, whereas many were weakly stained. Nerve fibres were found in the longitudinal muscle, circular muscle, muscularis mucosae and ganglia of the two plexuses. No nerve fibres were found in the lamina propria of the mucosa. The same distribution of nerve cells and fibres was revealed using immunohistochemistry for nitric oxide synthase. Lesion studies showed that the axons of myenteric neurons all projected anally. Myenteric cells were the source of nerve fibres in the circular muscle and in more anally located myenteric ganglia. The sparse innervation of submucous ganglia was intrinsic to the submucous plexus. It is suggested that nitric oxide synthase is one of the transmitters of inhibitory neurons to the muscle and is also utilized by descending interneurons of the myenteric plexus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Boeckxstaens GE, Pelckmans PA, Ruytjens IF, Bult H, De Man JG, Herman AG, Van Maercke YM (1991) Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction. Br J Pharmacol 103:1085–1091

    PubMed  CAS  Google Scholar 

  • Bredt DS, Snyder SH (1992) Nitric oxide, a novel neuronal messenger. Neuron 8:3–11

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS, Hwang PM, Snyder SH (1990) Localization of nitric oxide synthase indicating a neural role of nitric oxide. Nature 347:768–770

    Article  PubMed  CAS  Google Scholar 

  • Bornstein JC, Costa M, Furness JB, Lang RJ (1986) Electrophysiological analysis of projections of enteric inhibitory motorneurones in the guinea-pig small intestine. J Physiol (Lond) 370:61–74

    CAS  Google Scholar 

  • Bornstein JC, Furness JB, Smith TK, Trussell DC (1991) Synaptic responses evoked by mechanical stimulation of the mucosa in morphologically characterized myenteric neurons in the guinea pig ileum. J Neurosci 11: 505–518

    PubMed  CAS  Google Scholar 

  • Brookes SJH, Steele PAS, Costa M (1991) Identification and immunohistochemistry of cholinergic and non-cholinergic circular muscle motor neurons in the guinea-pig small intestine. Neuroscience 42:863–878

    Article  PubMed  CAS  Google Scholar 

  • Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Herman AG (1990) Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 345:346–347

    Article  PubMed  CAS  Google Scholar 

  • Burleigh DE (1992) Ng-nitro-L-arginine reduces non-adrenergic, non-cholinergic relaxations of human gut. Gastroenterology 102:679–683

    PubMed  CAS  Google Scholar 

  • Costa M, Furness JB (1976) The peristaltic reflex: an analysis of nerve pathways and their pharmacology. Naunyn-Schmiedeberg's Arch Pharmacol 294:47–60

    Article  CAS  Google Scholar 

  • Costa M, Furness JB (1983) The origins, pathways and terminations of neurons with VIP-like immunoreactivity in the guinea-pig small intestine. Neuroscience 8:665–676

    Article  PubMed  CAS  Google Scholar 

  • Costa M, Furness JB, Humphreys CMS (1986) Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract. Naunyn-Schmiedeberg's Arch Pharmacol 332:79–88

    Article  CAS  Google Scholar 

  • Costa M, Furness JB, Pompolo S, Brookes SJH, Bornstein JC, Bredt DS, Snyder SH (1992) Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. Neurosci Lett (in press)

  • Dalziel HH, Thornbury KD, Ward SM, Sanders KM (1991) Involvement of nitric oxide synthetic pathway in inhibitory junction potentials in canine proximal colon. Am J Physiol 260:G789-G792

    PubMed  CAS  Google Scholar 

  • Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801

    Article  PubMed  CAS  Google Scholar 

  • Desai KM, Zembowicz A, Sessa WC, Vane JR (1991) Nitroxergic nerves mediate vagally induced relaxation in the isolated stomach of the guinea pig. Proc Natl Acad Sci USA 88:11490–11494

    Article  PubMed  CAS  Google Scholar 

  • Furness JB, Costa M (1979) Projections of intestinal neurons showing immunoreactivity for vasoactive intestinal polypeptide are consistent with these neurons being the enteric inhibitory neurons. Neurosci Lett 15:199–204

    Article  PubMed  CAS  Google Scholar 

  • Furness JB, Bornstein JC, Murphy R, Pompolo S (1992a) Roles of peptides in transmission in the enteric nervous system. Trends Neurosci 15:66–71

    Article  PubMed  CAS  Google Scholar 

  • Furness JB, Pompolo S, Shuttleworth CWR, Burleigh DE (1992b) Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea pig caecum. Cell Tiss Res 270:125–137

    Article  CAS  Google Scholar 

  • Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends in Neurosci 14:60–67

    Article  CAS  Google Scholar 

  • Gillespie JS, Liu X, Martin W (1989) 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 98:1080–1082

    PubMed  CAS  Google Scholar 

  • Grider JR, Makhlouf GM (1986) Colonic peristaltic reflex: identification of vasoactive intestinal peptide as a mediator of descending relaxation. Am J Physiol 251:G40-G45

    PubMed  CAS  Google Scholar 

  • Grider JR, Murthy KS, Jin J-G, Makhlouf GM (1992) Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol 262:G774-G778

    PubMed  CAS  Google Scholar 

  • Gustafsson LE, Wiklund CU, Wiklund NP, Persson MG, Moncada S (1990) Modulation of autonomic neuroeffector transmission by nitric oxide in guinea pig ileum. Biochem Biophys Res Commun 173:106–110

    Article  PubMed  CAS  Google Scholar 

  • Hata F, Ishii T, Kanada A, Yamano N, Kataoka T, Takeuchi T, Yagasaki O (1990) Essential role of nitric oxide in descending inhibition in the rat proximal colon. Biochem Biophys Res Commun 172:1400–1406

    Article  PubMed  CAS  Google Scholar 

  • Hirst GDS, Holman M, McKirdy HC (1975) Two descending nerve pathways activated by distension of guinea-pig small intestine. J Physiol (Lond) 244:113–127

    CAS  Google Scholar 

  • Hope GT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814

    Article  PubMed  CAS  Google Scholar 

  • Hoyle CHV, Burnstock G (1989) Neuromuscular transmission in the gastrointestinal tract. In: Makhlouf GM (ed) Handbook of physiology, section 6. The gastrointestinal system, vol 1. American Physiological Society, Washington DC, pp 435–464

    Google Scholar 

  • Li CG, Rand MJ (1990) Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to the smooth muscle of the rat gastric fundus. Eur J Pharmacol 191:303–309

    Article  PubMed  CAS  Google Scholar 

  • Li ZS, Furness JB, Young HM, Campbell G (1992) Nitric oxide synthase immunoactivity and NADPH diaphorase enzyme activity in neurons of the gastrointestinal tract of the toad,Bufo marinus. Arch Histol Cytol 5:333–350

    Article  Google Scholar 

  • Llewellyn-Smith IJ, Furness JB, Gibbins JL, Costa M (1988) Quantitative ultrastructural analysis of enkephalin-, substance P-, and VIP-immunoreactive nerve fibers in the circular muscle of the guinea pig small intestine. J Comp Neurol 272:139–148

    Article  PubMed  CAS  Google Scholar 

  • Maccarrone C, Jarrott B (1985) Differences in regional brain concentrations of neuropeptide Y in spontaneously hypertensive (SH) and Wistar Kyoto (WKY) rat. Brain Res 345:165–169

    Article  PubMed  CAS  Google Scholar 

  • Maggi CA, Barbanti G, Turini D, Giuliani S (1991) Effect of Ng-monomethyl L-arginine (L-NMMA) and Ng-nitro L-arginine (L-NOARG) on non-adrenergic non-cholinergic relaxation in the circular muscle of the human ileum. Br J Pharmacol 103:1970–1972

    PubMed  CAS  Google Scholar 

  • Makhlouf GM, Grider JR, Shubert MC (1989) Identification of physiological function of gut peptides. In: Makhlouf GM (ed) Handbook of physiology, section 6. The gastrointestinal system, vol II. American Physiological Society, Washington DC, pp 123–131

    Google Scholar 

  • Messenger JP, Furness JB (1990) Projections of chemically-specified neurons in the guinea-pig colon. Arch Histol Cytol 53:467–495

    Article  PubMed  CAS  Google Scholar 

  • Murray J, Du C, Ledlow A, Bates JN, Conklin JL (1991) Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle. Am J Physiol 261:G401-G406

    PubMed  CAS  Google Scholar 

  • Niel JP, Bywater RAR, Taylor GS (1983) Apamin-resistant poststimulus hyperpolarization in the circular muscle of the guinea-pig ileum. J Autonom Nerv Syst 9:565–569

    Article  CAS  Google Scholar 

  • Osthaus LE, Galligan JJ (1992) Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of longitudinal muscle in guinea pig ileum. J Pharmacol Exp Ther 260:140–145

    PubMed  CAS  Google Scholar 

  • Rand MJ (1992) Nitrergic transmission: nitric oxide as a mediator of non-adrenergic, non-cholinergic neuroeffector transmission. Clin Exp Pharmacol Physiol 19:147–169

    Article  PubMed  CAS  Google Scholar 

  • Saffrey MJ, Hassall CJS, Hoyle CHV, Belai A, Moss J, Schmidt HHHW, Förstermann U, Murad F, Burnstock G (1992) Colocalization of nitric oxide synthase and NADPH-diaphorase in cultured myenteric neurones. Neuro Report 3:333–336

    CAS  Google Scholar 

  • Sanders KM, Ward SM (1992) Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 262:G379-G392

    PubMed  CAS  Google Scholar 

  • Scherer-Singler U, Vincent SR, Kimura H, McGeer EG (1983) Demonstration of a unique population of neurons with NADPH diaphorase histochemistry. J Neurosci Methods 9:229–234

    Article  PubMed  CAS  Google Scholar 

  • Shuttleworth CWR, Murphy R, Furness JB (1991) Evidence that nitric oxide participates in non-adrenergic inhibitory transmission to intestinal muscle in the guinea-pig Neurosci Lett 130:77–80

    Article  PubMed  CAS  Google Scholar 

  • Stark ME, Bauer AJ, Szurszewski JH (1991) Effect of nitric oxide on circular muscle of the canine small intestine. J Physiol (Lond) 444:743–761

    CAS  Google Scholar 

  • Stefanini M, De Martino C, Zamboni L (1967) Fixation of ejaculated spermatozoa for electron microscopy. Nature 216:173–174

    Article  PubMed  CAS  Google Scholar 

  • Thornbury KD, Ward SM, Dalziel HH, Carl A, Westfall DP, Sanders KM (1991) Nitric oxide and nitrosocysteine mimic nonadrenergic noncholinergic hyperpolarization in canine proximal colon. Am J Physiol 261:G553-G557

    PubMed  CAS  Google Scholar 

  • Toda N, Baba H, Okamura T (1990) Role of nitric oxide in nonadrenergic non-cholinergic nerve-mediated relaxation in dog duodenal longitudinal muscle strips. Jpn J Pharmacol 53:281

    Article  PubMed  CAS  Google Scholar 

  • Tottrup A, Knudsen MA, Gregersen H (1991) The role of the L-arginine-nitric oxide pathway in relaxation of the opossum lower ocsophageal sphincter. Br J Pharmacol 104:113–116

    PubMed  CAS  Google Scholar 

  • Vincent SR, Hope BT (1992) Neurons that say NO. Trends Neurosci 15:108–113

    Article  PubMed  CAS  Google Scholar 

  • Vincent SR, Kimura H (1992) Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience, 46:755–784

    Article  PubMed  CAS  Google Scholar 

  • Ward SM, Xue C, Shuttleworth CWR, Bredt DS, Snyder SH, Sanders KM (1992) NADPH diaphorase and nitric oxide synthase colocalization in enteric neurons of canine proximal colon. Am J Physiol (in press)

  • Will S, Bieger D, Triggle CR (1990) NO: possible role in TTX-sensitive field stimulated relaxations of the rat oesophageal tunica muscularis mucosae? Eur J Pharmacol 183:2419–2420

    Article  Google Scholar 

  • Young HM, Furness JB, Shuttleworth CWR, Bredt DS, Snyder SH (1992) Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine. Histochemistry 97:375–378

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Melbourne, 3052, Parkville, Australia

    K. McConalogue & J. B. Furness

Authors
  1. K. McConalogue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. B. Furness
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

McConalogue, K., Furness, J.B. Projections of nitric oxide synthesizing neurons in the guinea-pig colon. Cell Tissue Res 271, 545–553 (1993). https://doi.org/10.1007/BF02913739

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02913739

Key words

Search

Navigation