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The distribution of PKC isoforms in enteric neurons, muscle and interstitial cells of the human intestine

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Abstract

In many organs, different protein kinase C (PKC) isoforms are expressed in specific cell types, suggesting that the different PKCs have cell-specific roles, and also that drugs acting on a particular PKC may have effects on the whole organ that are distinguishable from drugs that target other isoforms. Previous studies of the guinea-pig and mouse intestine indicate that there are cell-specific expressions of PKC isoforms in neurons, muscle and the interstitial cells of Cajal. In the present study we have investigated the expression of different PKCs in human intestine. Immunohistochemical studies showed that the forms that are prominent in human enteric neurons are PKCs γ and ε and in muscle the dominant form is PKCδ. Neurons were weakly stained for PKCβI. These observations parallel findings in guinea-pig and mouse, except that in human PKCγ-IR was not present in the same types of neurons that express it in the guinea-pig. Enteric glial cells were strongly immunoreactive for PKCα, which is also the major isoform in enteric glial cells of guinea-pig. In human and guinea-pig, glial cells also express PKCβI. Spindle-shaped cells in the mucosa were immunoreactive for PKCα and PKCγ and in the muscle layers similar cells had PKCγ-IR and PKCθ-IR. The spindle-shaped cells were similar in morphology to interstitial cells of Cajal. Western analysis and RT-PCR confirmed the presence of the PKC isoform proteins and mRNA in the tissue. We conclude that there is cell-type specific expression of different PKCs in enteric neurons and intestinal muscle in human tissue, and that there are strong similarities in patterns of expression between laboratory animals and human, but some clear differences are also observed.

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References

  • Ali I, Sarna SK (2002) Selective modulation of PKC isozymes by inflammation in canine colonic circular muscle cells. Gastroenterology 122:483–494

    Article  PubMed  CAS  Google Scholar 

  • Bertrand PP, Galligan JJ (1995) Signal-transduction pathways causing slow synaptic excitation in guinea pig myenteric AH neurons. Am J Physiol 269:G710–G720

    PubMed  CAS  Google Scholar 

  • Blay P, Astudillo A, Buesa JM, Campo E, Abad M, García-García J, Miquel R, Marco V, Sierra M, Losa R, Lacave A, Braña A, Balbín M, Freije JMP (2004) Protein kinase C q is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias. Clin Cancer Res 10:4089–4095

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A, Croner R, Dimmler A, Papadopoulos T, Schrödl F, Neuhuber W (2004) Immunohistochemical characterization of putative primary afferent (sensory) myenteric neurons in human small intestine. Auton Neurosci 112:49–59

    Article  PubMed  CAS  Google Scholar 

  • Buéno L, Fioramonti J, Garcia-Villar R (2000) Pathobiology of visceral pain: molecular mechanisms and therapeutic implications III. Visceral afferent pathways: a source of new therapeutic targets for abdominal pain. Am J Physiol 278:G670–G676

    Google Scholar 

  • Cajal SRY (1893) Sur les ganglions et plexus nerveux de l’intestin. C R Soc Biol (Paris) 45:217–223

    Google Scholar 

  • Cajal SRY (1911) Histologie du système nerveux de l’homme et des vertébrés. Maloine, Paris

    Google Scholar 

  • Chang Q, Soper BD, Yacyshyn BR, Tepperman BL (2000) Alterations in protein kinase C isoforms in experimentally-induced colitis in the rat. Inflamm Res 49:27–35

    Article  PubMed  CAS  Google Scholar 

  • Corvera CU, Déry O, McConalogue K, Gamp P, Thoma M, Al-Ani B, Caughey GH, Hollenberg MD, Bunnett NW (1999) Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J Physiol 517:741–756

    Article  PubMed  CAS  Google Scholar 

  • Davidson LA, Jiang Y-H, Derr JN, Aukema HM, Lupton JR, Chapkin RS (1994) Protein kinase C isoforms in human and rat colonic mucosa. Arch Biochem Biophys 312:547–553

    Article  PubMed  CAS  Google Scholar 

  • Dekkers JA, Akkermans LM, Kroese AB (1997) Effects of the inflammatory mediator prostaglandin E2 on myenteric neurons in guinea pig ileum. Am J Physiol 272:G1451–G1456

    PubMed  CAS  Google Scholar 

  • Dorn GW, II Mochly-Rosen D (2002) Intracellular transport mechanisms of signal transducers. Annu Rev Physiol 64:407–429

    Article  PubMed  CAS  Google Scholar 

  • Goodnight J, Mischak H, Kolch W, Mushinski JF (1995) Immunocytochemical localization of eight protein kinase C isozymes overexpressed in NIH 3T3 fibroblasts. J Biol Chem 270:9991–10001

    Article  PubMed  CAS  Google Scholar 

  • Honjin R, Takahashi A, Tasaki Y (1965) Electron microscopic studies of nerve endings in the mucous membrane of the human intestine. Okajimas Folia Anat Jpn 40:409–427

    PubMed  CAS  Google Scholar 

  • Horowitz B, Ward SM, Sanders KM (1999) Cellular and molecular basis for electrical rhythmicity in gastrointestinal muscles. Annu Rev Physiol 61:19–43

    Article  PubMed  CAS  Google Scholar 

  • Hu HZ, Gao N, Liu S, Ren J, Xia Y, Wood DJ (2004) Metabotropic signal transduction for bradykinin in submucosal neurons of guinea pig small intestine. J Pharmacol Exp Ther 309:310–319

    Article  PubMed  CAS  Google Scholar 

  • Kawai M, Nguyen TV, Stebbing MJ, Clerc N, Komori S, Furness JB (2003) Comparison of effects of phorbol dibutyrate and of low frequency stimulation of synaptic inputs on currents that determine the excitability of myenteric AH neurons. Eur J Physiol 447:298–304

    Article  CAS  Google Scholar 

  • Kito Y, Fukuta H, Yamamoto Y, Suzuki H (2002) Excitation of smooth muscles isolated from the guinea-pig gastric antrum in response to depolarization. J Physiol 543.1:155–167

    Article  CAS  Google Scholar 

  • Klein IK, Ritland SR, Burgart LJ, Ziesmer SC, Roche PC, Gendler SJ, Karnes WE Jr (2000) Adenoma-specific alterations of protein kinase C isozyme expression in Apc MIN mice. Cancer Res 60:2077–2080

    PubMed  CAS  Google Scholar 

  • Komuro T, Tokui K, Zhou DS (1996) Identification of the interstitial cells of Cajal. Histol Histopathol 11:769–786

    PubMed  CAS  Google Scholar 

  • Komuro T, Seki K, Horiguchi K (1999) Ultrastructural characterization of the interstitial cells of Cajal. Arch Histol Cytol 62:295–316

    Article  PubMed  CAS  Google Scholar 

  • Linden DR, Sharkey KA, Mawe GM (2003) Enhanced excitability of myenteric AH neurones in the inflamed guinea-pig distal colon. J Physiol 547:589–601

    Article  PubMed  CAS  Google Scholar 

  • Nemeth PR, Ort CA, Wood JD (1984) Intracellular study of effects of histamine on electrical behaviour of myenteric neurones in guinea-pig small intestine. J Physiol 355:445–446

    Google Scholar 

  • Newton AC (1997) Regulation of protein kinase C. Curr Opin Cell Biol 9:161–167

    Article  PubMed  CAS  Google Scholar 

  • Nguyen TV, Poole DP, Harvey JR, Stebbing MJ, Furness JB (2005) Investigation of PKC isoform-specific translocation and targeting of the current of the late after hyperpolarising potential of myenteric AH neurons. Eur J Neurosci 21:905–913

    Article  PubMed  Google Scholar 

  • Palmer JM, Wong Riley M, Sharkey KA (1998) Functional alterations in jejunal myenteric neurons during inflammation in nematode-infected guinea pigs. Am J Physiol 275:G922–G935

    PubMed  CAS  Google Scholar 

  • Pan H, Wang HY, Friedman E, Gershon MD (1997) Mediation by protein kinases C and A of Go-linked slow responses of enteric neurons to 5-HT. J Neurosci 17:1011–1024

    PubMed  CAS  Google Scholar 

  • Poole DP, Hunne B, Robbins HL, Furness JB (2003) Protein kinase C isoforms in the enteric nervous system. Histochem Cell Biol 120:151–161

    Article  CAS  Google Scholar 

  • Poole DP, Nguyen TV, Kawai M, Furness JB (2004) Protein kinases expressed by interstitial cells of Cajal. Histochem Cell Biol 121:21 - 30

    Article  PubMed  CAS  Google Scholar 

  • Sakanoue Y, Hatada T, Horai T, Shoji Y, Kusunoki M, Utsunomiya J (1992) Protein kinase C activity of colonic mucosa in ulcerative colitis. Scand J Gastroenterol 27:275–280

    PubMed  CAS  Google Scholar 

  • Southwell BR (2003) Localization of protein kinase C theta immunoreactivity to interstitial cells of Cajal in guinea-pig gastrointestinal tract. Neurogastroenterol Motil 15:139–147

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Akimoto K, Ohno S (2003) Protein kinase C l/i (PKCl/i): A PKC isotype essential for the development of multicellular organisms. J Biochem (Tokyo) 133:9–16

    CAS  Google Scholar 

  • Thuneberg L (1982) The interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol 71:1–130

    PubMed  CAS  Google Scholar 

  • Tjwa ETTL, Bradley JM, Keenan CM, Kroese ABA, Sharkey KA (2003) Interleukin−1b activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon. Am J Physiol 285:G1268–G1276

    CAS  Google Scholar 

  • Torihashi S, Horisawa M, Watanabe Y (1999) c-kit immunoreactive interstitial cells in the human gastrointestinal tract. J Auton Nerv Syst 75:38–50

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto M, Sarna SK, Condon RE (1997) A novel motility effect of tachykinins in normal and inflamed colon. Am J Physiol 272:G1607–G1614

    PubMed  CAS  Google Scholar 

  • Vanderwinden JM, Rumessen JJ, Liu H, Descamps D, De Laet MH, Vanderhaeghen JJ (1996) Interstitial cells of Cajal in human colon and in Hirschsprung’s disease. Gastroenterology 111:901–910

    Article  PubMed  CAS  Google Scholar 

  • Wang XY, Ward SM, Gerthoffer WT, Sanders KM (2003) Protein kinase Ce translocation in enteric neurons and interstitial cells of Cajal in response to muscarinic stimulation. Am J Physiol 285:G593–G601

    CAS  Google Scholar 

  • Williamson S, Pompolo S, Furness JB (1996) GABA and nitric oxide synthase immunoreactivities are colocalized in a subset of inhibitory motor neurons of the guinea-pig small intestine. Cell Tissue Res 284:29–37

    Article  PubMed  CAS  Google Scholar 

  • Xia Y, Hu HZ, Liu S, Ren J, Zafirov DH, Wood JD (1999) IL-1b and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system. J Clin Invest 103:1309–1316

    Article  PubMed  CAS  Google Scholar 

  • Xiao J, Nguyen TV, Ngui K, Strijbos PJLM, Selmer I-S, Neylon CB, Furness JB (2004) Molecular and functional analysis of hyperpolarisation-activated nucleotide gated (HCN) channels in the enteric nervous system. Neuroscience 129:603–614

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National health and Medical Research Council of Australia and by Pfizer Pharmaceuticals, Japan.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, Parkville, VIC, 3010, Australia

    John B. Furness, Anderson J. Hind, Katrina Ngui, Heather L. Robbins & Daniel P. Poole

  2. Lab ITIS, UMR 6150 CNRS-Univ Méditerranée, Faculté de Médecine, Bd Pierre Dramard, Marseille, France

    Nadine Clerc & Thierry Merrot

  3. Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia

    Joseph J. Tjandra

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  1. John B. Furness
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  2. Anderson J. Hind
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  3. Katrina Ngui
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  4. Heather L. Robbins
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  5. Nadine Clerc
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  8. Daniel P. Poole
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Correspondence to John B. Furness.

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Furness, J.B., Hind, A.J., Ngui, K. et al. The distribution of PKC isoforms in enteric neurons, muscle and interstitial cells of the human intestine. Histochem Cell Biol 126, 537–548 (2006). https://doi.org/10.1007/s00418-006-0190-5

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  • DOI: https://doi.org/10.1007/s00418-006-0190-5

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