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GABA and Gut Motility

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GABA Outside the CNS

Abstract

Motility in the gut is a complex series of movements with an underlying orderliness that ensures descending propulsion of the intestinal contents.Prominent amongst these are rhythmic contractile activity and coordinated descending waves of contraction and relaxation. Rhythmic activity can occur in the absence of obvious stimulation but probably has a mixing function, whereas propulsive activity is triggered by distension or by chemical stimulation of the mucosa. There is an obvious polarity in the propulsive activity; contractions occur above the stimulated region and relaxation below. This is the basis of the peristaltic reflex [3] which persists in extrinsically denervated gut segments having no connections with the central nervous system. Indeed, isolated segments continue to exhibit a ränge of motility, including the peristaltic reflex, even when totally removed and maintained in artificial media. Such isolated preparations lend themselves to pharmacological investigation and have formed the basis of our studies on GABA involvement in motility patterns of the gut.

We are grateful to the Austraiian National Fellowship Advisory Committee for the award of a Queen Elizabeth II Research Fellowship to Jennifer Ong.

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References

  1. Andres-Trelles F, Bibby V, Lustman S, Simmonds MA (1989) Effects of cortisol on GABAA receptor-mediated responses compared in guinea-pig ileum and rat cuneate nucleus. Neuropharmacology 28: 705–708

    Article  PubMed  CAS  Google Scholar 

  2. Barajas-Lopez C, Berezin I, Daniel EE, Huizinga JD (1989) Pacemaker activity recorded in interstitial cells of Cajal of the gastrointestinal tract. Am J Physiol 257: C830–C835

    PubMed  CAS  Google Scholar 

  3. Bayliss WM, Starling EH (1899) The movements and innervation of the small intestine. J Physiol (Lond) 24: 99–143

    CAS  Google Scholar 

  4. Bowery NG, Hudson AL (1979) Gamma-aminobutyric acid reduces the evoked-release of [3H]-noradrenaiine from sympathetic nerve terminals. Br J Pharmacol 66: lO8P

    Google Scholar 

  5. Bowery NG, Doble A, Hill DR, Hudson AL, Shaw JS, Turnbull MJ, Warrington R (1981) Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol 71: 53–70

    Article  PubMed  CAS  Google Scholar 

  6. Brown DA, Marsh S (1978) Axonal GABA-receptors in mammalian peripheral nerve trunks. Brain Res 156: 187–191

    Article  PubMed  CAS  Google Scholar 

  7. Cherubini E, North RA (1984) Actions of gamma-aminobutyric acid on neurones of guinea-pig myenteric plexus. Br J Pharmacol 82: 93–100

    PubMed  CAS  Google Scholar 

  8. Cherubini E, North RA (1984) Inhibition of calcium spikes and transmitter release by gamma-aminobutyric acid in the guinea-pig myenteric plexus. Br J Pharmacol 82: 101–105

    PubMed  CAS  Google Scholar 

  9. Cherubini E, North RA (1985) Benzodiazepines both enhance gamma-aminobutyrate responses and decrease calcium action potential in guinea-pig myenteric neurones. Neuroscience 14: 309–315

    Article  PubMed  CAS  Google Scholar 

  10. Dogiel AS (1899) Ăœber den Bau der Ganglien in den Geflechten des Darmes und der Gallenblase des Menschen und der Säugetiere. Ach Anat Physiol 5: 130–159

    Google Scholar 

  11. Flachsenberger WA (1986) Studies on the peristaltic reflex. Thesis, University of Adelaide, Adelaide

    Google Scholar 

  12. Frigo GM, Lecchini S (1970) An improved method for studying the peristaltic reflex in the isolated colon. Br J Pharmacol 39: 346–356

    PubMed  CAS  Google Scholar 

  13. Frigo GM, Galli A, Lecchini S, Marcoli M (1987) A facilitatory effect of bicuculline on the enteric neurones in the guinea-pig isolated colon. Br J Pharmacol 90: 31–41

    PubMed  CAS  Google Scholar 

  14. Frye GD, Fincher AS, Lorenzetti M, Trzeciakowski J, Griffith WH (1990) Comparison of contractile responses of the guinea-pig ileum longitudinal muscle to ethänol and GABAA agonists. J Pharmacol Exp Ther 252: 474–481

    PubMed  CAS  Google Scholar 

  15. Furness JB, Trussell DC, Pompolo S, Bornsterin JC, Maley BE, Storm-Mathisen J (1989) Shapes and projections of neurons with immunoreactivity for gamma-aminobutyric acid in the guinea-pig small intestine. Cell Tissue Res 256: 293–301

    Article  PubMed  CAS  Google Scholar 

  16. Giotti A, Luzzi S, Spagnesi S, Zilletti L (1983) Homotaurine: a GABAB antagonist in guinea-pig ileum. Br J Pharmacol 79: 855–862

    PubMed  CAS  Google Scholar 

  17. Harrison NL, Simmonds MA (1984) Modulation of the GABA receptor complex by a Steroid anaesthetic. Brain Res 323: 287–292

    Article  PubMed  CAS  Google Scholar 

  18. Hashimoto S, Tanaka C, Taniyama K (1986) Presynaptic muscarinic and alphaadrenoceptor-mediated regulation of GABA release from myenteric neurones of the guinea-pig small intestine. Br J Pharmacol 89: 787–792

    PubMed  CAS  Google Scholar 

  19. Hill DR, Bowery NG (1981) 3H-Baclofen and 3H-GABA bind to bicuculline-insensitive GABAB sites in rat brain -Nature 290: 149–152

    Google Scholar 

  20. Hobbiger F (1958) Effects of gamma-aminobutyric acid on the isolated mammalian ileum. J Phyiol (Lond) 142: 147–164

    CAS  Google Scholar 

  21. Hobbiger F (1958) Antagonism by gamma-aminobutyric acid to the actions of 5-hydroxytryptamine and nicotine in isolated organs. J Physiol (Lond) 144: 349–360

    CAS  Google Scholar 

  22. Huizinga JD, Berezin I, Daniel EE, Chow E (1990) Inhibitory innervation of colonic smooth muscle cells and interstitial cells of Cajal. Can J Physiol Pharmacol 68: 447–454

    Article  PubMed  CAS  Google Scholar 

  23. Inouye A, Fukuya M, Tsuchiya K, Tsujioka T (1960) Studies on the effects of gammaaminobutyric acid on the isolated guinea-pig ielum. J Physio (Jap) 10: 167–182

    CAS  Google Scholar 

  24. Jesse KR, Hills JM, Saffrey MJ (1986) Immunohistochemical demonstration of GABAergic neurons in the enteric nervous system. J Neuroscience 6: 1628–1634

    Google Scholar 

  25. Jessen KR, Mirsky R, Dennison ME, Burnstock G (1979) GABA may be a neurotransmitter in the vertebrate peripheral nervous system. Nature 281: 71–74

    Article  PubMed  CAS  Google Scholar 

  26. Johnston GAR, Kerr DIB, Ong J (1987)Stress, steroids and GABA receptors. In: Rand MJ, Raper C. (eds) Elsevier, Amsterdam, pp 121–124

    Google Scholar 

  27. Kaplita PV, Waters DM, Triggle DJ (1982) Gamma-aminobutyric acid action in guinea-pig ileal myenteric plexus. Eur J Pharmacol 79: 43–51

    Article  PubMed  CAS  Google Scholar 

  28. Kerr DIB, Ong J (1984) Evidence that ethylenediamine acts in the isolated ileum of the guinea-pig by releasing endogenous GABA. Br J Pharmacol 83: 169–177

    PubMed  CAS  Google Scholar 

  29. Kerr DIB, Ong J (1986) Gamma-aminonutyric acid-dependent motility induced by avermectin Bla in the isolated intestine of the guinea-pig. Neurosci Lett 65: 7–10

    Article  PubMed  CAS  Google Scholar 

  30. Kerr DIB, Ong J (1986) GABAergic mechanisms in the gut: their role in the reglation of gut motility. In: Erdö SL, Bowery NG. (eds) GABAergic mechanisms in the mammalian periphery. Raven, New York

    Google Scholar 

  31. Kerr DIB, Ong J (1989) GABAB receptors in peripheral function. In: Bowery NG, Nistico G. (eds) GABA: basic research and clinical applications. Phytagora, Rome, pp 239–259

    Google Scholar 

  32. Kerr DIB, Ong J, Prager RH (1990) Antagonism of GABAB receptor-mediated responses in the guinea-pig isolated ileum and vas deferens by phosphono-analogues of GABA. Br J Pharmacol 99: 422–426

    PubMed  CAS  Google Scholar 

  33. Kerr DIB, Ong J, Prager RH Ward DA (1986) Caprolactam-barbiturate interaction at the GABAA receptor compiex in the guinea-pig intestine. Eur J Pharmacol 124: 203–206

    Article  PubMed  CAS  Google Scholar 

  34. Kerr DIB, Ong J, Prager RH, Gynther BD, Curtis DR (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res 405: 150–154

    Article  PubMed  CAS  Google Scholar 

  35. Kerr DIB, Ong J, Johnston GAR, Abbenante J, Prager RH (1988) 2-Hydroxysaclofen: an improved antagonist at central and peripheral GABAB receptors. Neurosci Lett 92: 92–96

    Article  PubMed  CAS  Google Scholar 

  36. Kerr DIB, Ong J, Johnston GAR, Abbenante J, Prager RH (1989) Antagonism at GABA B receptors by saclofen and related sulphonic analogues of baclofen and GABA. Neurosci Lett 107: 239–244

    Article  PubMed  CAS  Google Scholar 

  37. Kerr DIB, Ong J, Johnston GAR, Berthelot P, Debaert M, Vaccher C (1989) Benzofuran analogues of baclofen: a new class of central and peripheral GABAB receptor antagonists. Eur J Pharmacol 164: 361–364

    Article  PubMed  CAS  Google Scholar 

  38. Krantis A, Harding RKH (1987) GABA-related actions in isolated in vitro preparations of the rat small intestine. Eur J Pharmacol 141: 291–298

    Article  PubMed  CAS  Google Scholar 

  39. Krantis A, Kerr DIB (1981) Autoradiographic Iocalisation of 3H-gamma aminobutyric acid in the myenteric plexus of the guinea-pig small intestine. Neurosci Lett 23: 263–268

    Article  PubMed  CAS  Google Scholar 

  40. Krantis A, Kerr DIB (1981) GABA induced excitatory responses in the guinea-pig small intestine are antagonized by bicuculline, picrotoxinin and Chloride ion blockers. NaunynSchmiedebergs Arch Pharmacol 317: 257–262

    Article  PubMed  CAS  Google Scholar 

  41. Krantis A, Kerr DIB (1981) The effect of GABA antagonism on propulsive activity of the guinea-pig large intestine. Eur J Pharmacol 76: 111–114

    Article  PubMed  CAS  Google Scholar 

  42. Krantis A, Kerr DIB, Dennis BJ (1986) Autoradiographic study of the distribution of [3H] gamma aminobutyrate-accumulating neural elements in guinea-pig intestine: evidence for a transmitter function for gamma-aminobutyre. Neuroscience 17: 1243–1255

    Article  PubMed  CAS  Google Scholar 

  43. Krantis A, Costa M Furness JB, Orbach J (1980) γ-Aminobutyric acid stimulates intrinsic inhibitory and excitatory nerves in the guinea-pig intestine. Eur J Pharmacol 67: 461–468

    Article  PubMed  CAS  Google Scholar 

  44. Langley JN (1921) The autonomic nervous system, Part I. Heffer, London

    Google Scholar 

  45. Luzzi S, Spagnesi S, Franchi-Micheli S, Rosi E, Ciuffi M, Zilletti L (1986) Diazepam potentiates GABA-contraction in guinea-pig ileum. Arch Int Pharmacodyn Ther 279: 29–39

    PubMed  CAS  Google Scholar 

  46. Micheletti A, Schiavone A, Giachetti A (1988) Muscarinic Ml receptors stimulate a nonadrenergic noncholinergic inhibitory pathway in the isolated rat duodenum. J Pharmacol Exp Ther 244: 680–684

    PubMed  CAS  Google Scholar 

  47. Muhyaddin M, Roberts PJ, Woodruff GN (1982) Presynaptic gamma-aminobutyric acid receptors in the rat anococcygeus muscle and their antagonism by 5-aminovaleric acid. Br J Pharmacol 77: 163–168

    PubMed  CAS  Google Scholar 

  48. Nakamoto M, Tanaka C, Taniyama K (1987) Release of gamma-aminobutyric acid and acetylocholine by neurotensin in the guinea pig ileum. Br J Pharmacol 90: 545–551

    PubMed  CAS  Google Scholar 

  49. Olsen RW. (1981) GABA benzodiazapines-barbiturate receptor interactions. J Neurochem 37: 1–13

    Article  PubMed  CAS  Google Scholar 

  50. Ong J (1987) Uptake inhibitors potentiate gamma-aminobutyric acid-induced contractile responses in the isolated ileum of the guinea-pig. Br J Pharmacol 91: 9–15

    PubMed  CAS  Google Scholar 

  51. Ong J, Kerr DIB (1983) GABAA and GABAB receptor-mediated modification of intestinal motility. Eur J Pharmacol 86: 9–17

    Article  Google Scholar 

  52. Ong J, Kerr DIB (1983) Interaction between GABA and 5-hydroxytryptamine in the guinea-pig ileum. Eur J Pharmacol 94: 305–312

    Article  PubMed  CAS  Google Scholar 

  53. Ong J, Kerr DIB (1984) Evidence for a physiological role of GABA in the control of guinea-pig intestinal motility. Neurosci Lett 50: 339–343

    Article  PubMed  CAS  Google Scholar 

  54. Ong J, Kerr DIB (1984) Potentiation of GABAA receptor-mediated responses by harbiturates in the guinea-pig ileum. Eur J Pharmacol 103: 327–332

    Article  PubMed  CAS  Google Scholar 

  55. Ong J, Kerr DIB (1984) Evidence that 5-hydroxytryptamine does not mediate GABAinduces contractile responses in the guinea-pig proximal ileum. Eur J Pharmacol 106: 665–668

    Article  PubMed  CAS  Google Scholar 

  56. Ong J, Kerr DIB (1987) Comparison of GABA-induced responses in various segments of the guinea-pig intestine. Eur J Pharmacol 134: 349–353

    Article  PubMed  CAS  Google Scholar 

  57. Ong J, Kerr DIB (1989) GABAergic modulation of spontaneous motility in the guineapig isolated intestine. Neurosci Lett 101: 203–208

    Article  PubMed  CAS  Google Scholar 

  58. Ong J, Kerr DIB. (1990) GABA receptors in peripheral tissues. Life Sei 46: 1489–1501

    Article  CAS  Google Scholar 

  59. Ong J, Kerr DIB, Johnston GAR (1987) Calcium-dependence of baclofen- and GABAinduced depression of responses to transmural Stimulation in the guinea-pig isolated ileum. Eur J Pharmacol 134: 369–372

    Article  PubMed  CAS  Google Scholar 

  60. Ong J, Kerr DIB, Johnston GAR (1987) Cortisol: a potent biphasic modulator at GABAA receptor complexes in the guinea-pig isolated ileum. Neurosci Lett 82: 101–106

    Article  PubMed  CAS  Google Scholar 

  61. Ong J, Kerr DIB, Johnston GAR (1987) Pregnenolone and its sulphate modulate GABAA receptor-mediated contractile responses in the guinea-pig isolated ileum. Eur J Pharmacol 142: 461–464

    Article  PubMed  CAS  Google Scholar 

  62. Ong J, Kerr DIB, Johnston. (1988) Alfaxalone potentiates and mimics GABA-induced contractile responses in the guinea-pig isolated ileum. Br J Pharmacol 95: 33–38

    PubMed  CAS  Google Scholar 

  63. Ong J, Harrison NL, Hall RG, Barker JL, Johnston GAR, Kerr DIB (1990) 3-Aminopropanephosphinic acid is a potent agonist at peripheral and central presynaptic GABAB receptors. Brain Res (to be published)

    Google Scholar 

  64. Pong SS, Wang CC, Fritz LC (1980) Studies on the mechanism of action of avermectin Bla: Stimulation of release of gamma-aminobutyric acid from brain synaptosomes. J Neurochem 34: 351–358

    Article  PubMed  CAS  Google Scholar 

  65. Schworer H, Kilbinger H (1988) Enhancement of guinea-pig intestinal peristalsis by blockade of muscarinic Ml-receptors. Br J Pharmacol 93: 715–720

    PubMed  CAS  Google Scholar 

  66. Shirakawa J, Takeda K, Taniyama K, Tanaka C (1989) Dual effects of 5-hydroxytryptamine on the release of gamma-aminobutyric acid from myenteric neurones of the guinea-pig ileum. Br J Pharmacol 98: 339–341

    PubMed  CAS  Google Scholar 

  67. Study RE, Barker JL (1981) Diazepam and (-)pentobarbital-fluctuation analysis reveals different mechanisms for potentiation of GABA responses in cultured central neurones. Proc Natl Acad Sei USA 78: 7180–7184

    Article  CAS  Google Scholar 

  68. Tanaka C, Taniyama K (1985) Substance P provoked gamma-aminobutyric acid release from the myenteric plexus of the guinea-pig small intestine. J Physiol (Lond) 362: 319–329

    CAS  Google Scholar 

  69. Tanaka C, Taniyama K (1986) GABA transport in peripheral tissues; uptake and efflux. In: Erdö SL, Bowery NG (eds) GABAergic mechanisms in the mammalian periphery. Raven, New York, pp 57–75

    Google Scholar 

  70. Taniyama K, Hashimoto S, Hanada S, Tanaka C (1988) Benzodiazepines and barbiturate potentiate the pre- and postsynaptic gamma-aminobutyric acid (GABA)-A receptor-mediated response in the enteric nervous system of guinea-pig small intestine. J Pharmacol Exp Ther 245: 250–256

    PubMed  CAS  Google Scholar 

  71. Ticku MK, Lowrimore P, Lehoullier P (1986) Ethanol enhances GABA-induced 36Clinflux in primary spinal cord cultured neurons. Brain Res Bull 17: 123–126

    Article  PubMed  CAS  Google Scholar 

  72. Tonini M, De Petris G, Onori L, Manzo L, Rizzi CA, Crema A (1989) The role of GABAA receptor function in peristaltic activity of the guinea-pig ileum: a comparative study with bicuculline, SR 95531 and picrotoxinin.Br J Pharmacol 97: 556–562

    PubMed  CAS  Google Scholar 

  73. Tonini M, Onori L, Lecchini S, Frigo GM, Perucca E, Saltarelli P, Crema A (1983) 5-HT mediated GABA excitatory responses in the guinea-pig proximal ileum. Naunyn-Schmiedebergs Arch Pharmacol 324: 180–184

    Article  PubMed  CAS  Google Scholar 

  74. Tonini M, Onori L, Rizzi CA, De Ponti F, Perucca E, Budassi P, Crema A (1986) Inhibitory action of capsaicin on cholinergic responses induced by GABAA agonists in the guinea-pig ileum. Eur J Pharmacol 128: 273–276

    Article  PubMed  CAS  Google Scholar 

  75. Tonini M, Onori L, Rizzi CA, De Ponti F, Perucca E, Budassi P, Crema A (1987) Involvement of substance P in the excitatory action of GABAA agonists on cholinergic neurons in the guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol 335: 629–635

    Article  PubMed  CAS  Google Scholar 

  76. Tonini M, Onori L, Manzo L, Rizzi CA, Crema A (1988) Cholinergic contractions induced by GABAA receptor activation in the guinea-pig ileum are inhibited by alphachymotrypsin and potentiated by diazepam. Arch Int Pharmacodyn Ther 296: 173–183

    PubMed  CAS  Google Scholar 

  77. Tonini M, Saltarelli P, Onori L, De Ponti F, Garlaschelli L, Rizzi CA, Crema A (1986) A re-appraisal of the mode of action of 5-HT in inhibiting GABA-induced cholinergic contractions in the guinea-pig ileum. Eur J Pharmacol 127: 267–270

    Article  PubMed  CAS  Google Scholar 

  78. Wood JD (1983) Neurophysiology of parasympathetic and enteric ganglia. In: Lars-Gosta (ed) Autonomic ganglia. John Wiley, Chichester, pp 367–398

    Google Scholar 

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Kerr, D.I.B., Ong, J. (1992). GABA and Gut Motility. In: Erdö, S.L. (eds) GABA Outside the CNS. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76915-3_3

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  • DOI: https://doi.org/10.1007/978-3-642-76915-3_3

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