Effects of ${\gamma}-Aminobutyric$ Acid on Pancreatic Amylase Secretion Evoked by Sodium Oleate in Anesthetized Rats

  • Park, Yong-Deuk (Department of Physiology, College of Medicine, and Institute of Environment and Life Science, The Hallym Academy of Science, Hallym University) ;
  • Cui, Zheng-Yun (Department of Physiology, College of Medicine, and Institute of Environment and Life Science, The Hallym Academy of Science, Hallym University) ;
  • Park, Hyung-Seo (Department of Physiology, College of Medicine, Konyang University) ;
  • Park, Hyoung-Jin (Department of Physiology, College of Medicine, and Institute of Environment and Life Science, The Hallym Academy of Science, Hallym University)
  • Published : 2002.02.21

Abstract

${\gamma}-Aminobutyric$ Acid (GABA) is contained in pancreatic islet ${\beta}-cells$ although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h),$ given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA $(30\;{\mu}mol/kg/h)$ also further increased the amylase secretion stimulated by CCK (30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h)$ also dose-dependently elevated pancreatic amylase secretion evoked by CCK alone. Bicuculline $(100\;{\mu}mol/kg/h),$ a $GABA_A-receptor$ antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK plus secretin or CCK alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via $GABA_A-receptor$ in anesthetized rats, which may account for elevating the action of CCK released by sodium oleate.

References

  1. Von Blankenfeld G, Turner J, Ahnert-Hilger G, John M, Enkvist MO, Stephenson F, Kettenmann H, Wiedenmann B. Expression of functional GABAA receptors in neuroendocrine gastropancreatic cells. Pflgers Arch-Eur J Physiol 430: 381-388, 1995
  2. Cherubini E, North RA. r-Aminobutyric acid actions on neurons of guinea-pig myenteric plexus. Br J Phannacol 82: 93-100, 1984
  3. Garry DJ, Sorenson RL, Elde RP, Maley BE, Madsen A. Immunohistochemical colocalization of GABA and insulin in beta-cells of rat islet. Diabetes 35: 1090-1095, 1986
  4. Gaskins HR, Baldeon ME, Selassie L, Beverly JL. Glucose modulates gamma-aminobutyric acid release from the pancreatic beta TC6 cell line. Bioi Chern 270: 30286-30289, 1995
  5. Gerber JC, Hare TA. GABA in peripheral tissues: Presence and action in pancreatic function. Brain Res Bull (Suppl 2) 5: 341-346, 1980
  6. Gilon P, Bertrand G, Loubatieres-Mariani MM, Remade C, Henquin JC. The influence of gamma-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas. Endocrinology 129: 2521-2529, 1991
  7. Henderson JR, Daniel PM. A comparative study of the portal vessels connecting the endocrine and exocrine pancreas, with a discussion of some functional implications. QJ Exp Physiol Cogn Med Sci 64: 267-275, 1979
  8. Li P, Lee KY, Chang T-M, Chey WY. Hormonal mechanism of sodium oleate-stimulated pancreatic secretion in rats. Am J Physiol (Gastraintest Liver Physiol 22) 259: G960-G965, 1990
  9. Lifson N, Lassa CV, Dixit PK. Relation between blood flow and morphology in islet organ of rat pancreas. Am J Physiol (Endocrinol Metab 12) 249: E43-E48, 1985
  10. Michalik M, Nelson J, Erecinska M. GABA production in rat islets of Langerhans. Diabetes 42: 1506-1513, 1993
  11. Okada Y, Taniguchi H, Schimada C. High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Science 194: 620-622, 1976
  12. Park HS, Kwon HY, Lee YL, Chey WY, Park HJ. Role of GRPergic neurons in secretin-evoked exocrine secretion in isolated rat pancreas. Am J Physiol Gastraintest Liver Physiol 278: G557-G562, 2000
  13. Park HS, Park HJ. Effects of r-aminobutyric acid on secretagogueinduced exocrine secretion of isolated, perfused rat pancreas. Am J Physiol Gastraintest Liver Physiol 279: G677-G682, 2000
  14. Reetz A, Solimena M, Matteoli M, Folli F, Takei K, De Camilli P. GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesides suggests their role in GABA storage and secretion. EMBO J 10: 1275-1284, 1991
  15. Reusens-Billen B, Pirlot X, Remade C, Holst JJ, De Gasparo M. Localization of GABA high-affinity binding sites in the pancreas of neonatal rat. Cell Tissue Res 235: 503-508, 1984
  16. Rick W, Stegbauer HP. a-Amylase; measurement of reducing group. In: Bergermeyer HU, ed, Method of Enzymatic Analysis, Volume 2, 2nd ed., Verlag Chemie, Weiheim, Germany, p 885-915, 1974
  17. Robbins MS, Grouse LH, Sorenson RL, Elde RP. Effect of muscimol on glucose-stimulated somatostatin and insulin release from the isolated, perfused rat pancreas. Diabetes 30: 168-171, 1981
  18. Rorsman P, Berggren P-O, Bokvist K, Ericson H, Mohler H, Ostenson CoG, Smith PA. Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. Nature 341: 233-236, 1989
  19. Sakaue M, Saito N, Tanaka C. Immunohistochemical localization of gamma-aminobutyric acid (GABA) in the rat pancreas. Histochemistry 86: 365-369, 1987
  20. Schwartz RD. The GABAA receptor-gated ion channel: biochemical and pharmacological studies of structure and function. Biochem Pharrnacol 37: 3369-3375, 1988
  21. Smismans A, Schuit F, Pipeleers D. Nutrient regulation of gammaaminobutyric acid release from islet beta cell. Diabetologia 40: 1411-1415, 1997
  22. Sorenson RL, Garry DG, Brelje TC. Structural and functional considerations of GABA in islets of Langerhans. p-cells and nerves. Diabetes 40: 1365-1374, 1991
  23. Vincent SR, Hokfelt T, Wu JY, Elde RP, Morgan LM, Kimmel JR. Immunohistochemical studies of the GABA system in the pancreas. Neuraendocrinology 36: 197-204, 1983