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Electrically stimulated relaxation is not mediated by GABA in cat lower esophageal sphincter muscle

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Abstract

This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin (10−6 M) suppressed the electrically stimulated (0.5–5 Hz) relaxation of the LES. However, guanethidine (10−6 M) and atropine (10−6 M) had no effect indicating that the relaxations were neurally mediatedvia the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester (10−4 M, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60% inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA (10−3–10−5 M, non selective receptor agonist), muscimol (10−3–10−5 M, GABA-A agonist), and baclofen (10−3–10−5 M, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline (10−5 M, GABA-A antagonist) and phaclofen (10−5 M, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.

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References

  • Akinci, M. K. and Schofield, P. R., Widespread expression of GABA(A) receptor subunits in peripheral tissues.Neurosci Res., 35, 145–153 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Biancani, P., Walsh, J. H., and Behar, J., Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation.J. Clin. Invest., 73, 963–967 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Brookes, S. J., Chen, B. N., Hodgson, W. M., and Costa, M., Characterization of excitatory and inhibitory motor neurons to the guinea pig lower esophageal sphincter.Gastroenterology, 111, 108–117 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Devlin, C. L. and Schlosser, W., Gamma-aminobutyric acid modulation of acetylcholine-induced contractions of a smooth muscle from an echinoderm (Sclerodactyla briareus).Invert Neurosci., 4, 1–8 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Goyal, R. K., Rattan, S., and Said, S. I., VIP as a possible neurotransmitter of non-cholinergic non-adrenergic inhibitory neurones.Nature, 288, 378–380 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Hebeiss, K. and Kilbinger, H., Cholinergic and GABAergic regulation of nitric oxide synthesis in the guinea pig ileum.Am. J. Physiol., 276, G862–866 (1999).

    PubMed  CAS  Google Scholar 

  • Jury, J., Ahmedzadeh, N., and Daniel, E. E., A mediator derived from arginine mediates inhibitory junction potentials and relaxations in lower esophageal sphincter: an independent role for vasoactive intestinal peptide.Can J. Physiol. Pharmacol., 70, 1182–1189 (1992).

    PubMed  CAS  Google Scholar 

  • Kerr, D. I. and Krantis, A., Uptake and stimulus-evoked release of [3H]-gamma-aminobutyric acid by myenteric nerves of guinea-pig intestine.Br. J. Pharmacol., 78, 271–276 (1983).

    PubMed  CAS  Google Scholar 

  • Kilbinger, H., Ginap, T., and Erbelding, D., GABAergic inhibition of nitric oxide-mediated relaxation of guinea-pig ileum.Naunyn Schmiedebergs Arch. Pharmacol., 359, 500–504 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Kortezova, N., Mizhorkova, Z., Milusheva, E., Varga, G., Vizi, E. S., and Papasova, M., Non-adrenergic non-cholinergic neuron stimulation in the cat lower esophageal sphincter.Eur. J. Pharmacol., 304, 109–115 (1996).

    Article  PubMed  CAS  Google Scholar 

  • McDermott, C. M., Abrahams, T. P., Partosoedarso, E., Hyland, N., Ekstrand, J., Monroe, M., and Hornby, P. J., Site of action of GABA(B) receptor for vagal motor control of the lower esophageal sphincter in ferrets and rats.Gastroenterology, 120, 1749–1762 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Murr, M. M., Balsiger, B. M., Farrugia, G., and Sarr, M. G., Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum.J. Surg. Res., 84, 8–12 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Seelig, L. L. Jr. and Goyal, R. K., Morphological evaluation of opossum lower esophageal sphincter.Gastroenterology, 75, 51–58 (1978).

    PubMed  Google Scholar 

  • Tohda, Y., Ohkawa, K., Kubo, H., Muraki, M., Fukuoka, M., and Nakajima, S., Role of GABA receptors in the bronchial response: studies in sensitized guinea-pigs.Clin Exp. Allergy., 28, 772–777 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Tottrup, A., Svane, D., and Forman, A., Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter.Am. J. Physiol., 260, G385–389 (1991).

    PubMed  CAS  Google Scholar 

  • Uc, A., Murray, J. A., and Conklin, J. L., Effects of calcitonin gene-related peptide on opossum esophageal smooth muscle.Gastroenterology, 113, 514–520 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Uc, A., Oh, S. T., Murray, J. A., Clark, E., and Conklin, J. L., Biphasic relaxation of the opossum lower esophageal sphincter: roles of NO., VIP, and CGRP.Am. J. Physiol., 277, G548–554 (1999).

    PubMed  CAS  Google Scholar 

  • Williamson, S., Faulkner-Jones, B. E., Cram, D. S., Furness, J. B., and Harrison, L. C., Transcription and translation of two glutamate decarboxylase genes in the ileum of rat, mouse and guinea pig.J. Auton. Nerv. Syst., 55, 18–28 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Williamson, S., Pompolo, S., and Furness, J. B., 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 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Yamato, S., Saha, J. K., and Goyal, R. K., Role of nitric oxide in lower esophageal sphincter relaxation to swallowing.Life Sci., 50, 1263–1272 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Yuan, S., Costa, M., and Brookes, S. J., Neuronal pathways and transmission to the lower esophageal sphincter of the guinea Pig.Gastroenterology, 115, 661–671 (1998).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Uy Dong Sohn.

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Park, S.Y., Shin, C.Y., Song, H.J. et al. Electrically stimulated relaxation is not mediated by GABA in cat lower esophageal sphincter muscle. Arch Pharm Res 29, 400–404 (2006). https://doi.org/10.1007/BF02968590

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