Gamma-aminobutyric acid secreted from islet beta-cells modulates exocrine secretion in rat pancreas.
OBJECTIVE
To investigate the role of endogenous gamma-amino-butyric acid (GABA) in pancreatic exocrine secretion.


METHODS
The isolated, vascularly perfused rat pancreas was employed in this study to eliminate the possible influences of extrinsic nerves and hormones. Cholecystokinin (CCK; 10 pmol/L) was intra-arterially given to stimulate exocrine secretion of the pancreas.


RESULTS
Glutamine, a major precursor of GABA, which was given intra-arterially at concentrations of 1, 4 and 10 mmol/L, dose-dependently elevated the CCK-stimulated secretions of fluid and amylase in the normal pancreas. Bicuculline (10 micromol/L), a GABA(A) receptor antagonist, blocked the enhancing effect of glutamine (4 mmol/L) on the CCK-stimulated exocrine secretions. Glutamine, at concentrations of 1, 4 and 10 mmol/L, dose-dependently increased the GABA concentration in portal effluent of the normal pancreas. The effects of glutamine on the CCK-stimulated exocrine secretion as well as the GABA secretion were markedly reduced in the streptozotocin-treated pancreas.


CONCLUSIONS
GABA could be secreted from beta-cells into the islet-acinar portal system after administration of glutainine, and could enhance the CCK-stimulated exocrine secretion through GABA(A) receptors. Thus, GABA in islet beta-cells is a hormone modulating pancreatic exocrine secretion.
Park
Yong-Deuk
YD
Department of MedicoLife Science, Youngdong University, Chungbuk, Korea.
Cui
Zheng-Yun
ZY
Wu
Guang
G
Park
Hyung-Seo
HS
Park
Hyoung-Jin
HJ
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005973:Glutamine / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008297:Male; D046790:Pancreas, Exocrine / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000032:analysis / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D001640:Bicuculline