Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Electrically Stimulated Relaxation is not Mediated by GABA in Cat Lower Esophageal Sphincter Muscle

  • Park Sun-Young (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • Shin Chang-Yell (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • Song Hyun-Ju (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • Min Young-Sil (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • La Hyen-O (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Lee Jun-Woo (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • Kim Do-Young (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • Je Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Sohn Uy-Dong (Department of Pharmacology, College of Pharmacy, Chung Ang University)
  • Published : 2006.05.01
Download PDF
⟨ Previous Next ⟩

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 mediated via 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.

Keywords

References

  1. Akinci, M. K. and Schofield, P. R., Widespread expression of GABA(A) receptor subunits in peripheral tissues. Neurosci Res., 35, 145-153 (1999) https://doi.org/10.1016/S0168-0102(99)00078-4
  2. 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) https://doi.org/10.1172/JCI111320
  3. 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) https://doi.org/10.1053/gast.1996.v111.pm8698189
  4. 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) https://doi.org/10.1007/s101580050001
  5. 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) https://doi.org/10.1038/288378a0
  6. 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)
  7. 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) https://doi.org/10.1139/y92-164
  8. 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) https://doi.org/10.1111/j.1476-5381.1983.tb09391.x
  9. 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) https://doi.org/10.1007/PL00005382
  10. 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) https://doi.org/10.1016/0014-2999(96)00093-3
  11. 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) https://doi.org/10.1053/gast.2001.24849
  12. 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) https://doi.org/10.1006/jsre.1999.5590
  13. Seelig, L. L. Jr. and Goyal, R. K., Morphological evaluation of opossum lower esophageal sphincter. Gastroenterology, 75, 51-58 (1978)
  14. 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) https://doi.org/10.1046/j.1365-2222.1998.00289.x
  15. Tottrup, A., Svane, D., and Forman, A., Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am. J. Physiol., 260, G385-389 (1991)
  16. 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) https://doi.org/10.1053/gast.1997.v113.pm9247471
  17. 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)
  18. 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) https://doi.org/10.1016/0165-1838(95)00028-V
  19. 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) https://doi.org/10.1007/s004410050564
  20. 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) https://doi.org/10.1016/0024-3205(92)90326-K
  21. 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) https://doi.org/10.1016/S0016-5085(98)70145-3