Effects of intracerebroventricular injection of glucagon like peptide-1 and its related peptides on serotonin metabolism and on levels of amino acids in the rat hypothalamus.
High concentrations of glucagon-like peptide-1 (7-36) amide (GLP-1) and its specific receptor (GLP-1R) have been found in the rat hypothalamus. In this study the actions of GLP-1 and its related peptides, exendin-4 (GLP-1R agonist), exendin (9-39) (GLP-1R antagonist) and GLP-1 (9-36) amide (the major GLP-1 metabolite) on levels of serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA) and amino acids (Glu, Asp, Gln, Gly, Tyr, Trp, GABA) in the hypothalamus were investigated. Intracerebroventricular (ICV) injection of GLP-1 (4 nmol) produced a significant reduction in levels of 5-HT (54%) and all measured amino acids (34 to 56%) compared with saline injected controls, whereas exendin (9-39) (4 nmol) was ineffective. ICV injection of exendin-4 produced a significant reduction in the levels of 5-HT, 5-HIAA, Trp, Glu, and Tyr. ICV injection of GLP-1(9-36) amide showed a statistically significant increase in the level of 5-HT, 5-HIAA and all the amino acids tested in this study. Prior administration of exendin (9-39) or GLP-1 (9-36) amide blocked the effects of GLP-1 on the levels of 5-HT and the amino acids. These data are consistent with exendin-4 being a GLP-1R agonist and exendin (9-39) being a specific GLP-1R antagonist. GLP-1 (9-36) amide, a primary metabolite of GLP-1, appears to act as an endogenous antagonist at the GLP-1R.
Owji
A A
AA
Department of Biochemistry, Shiraz University of Medical Sciences, P.O. Box 1971, Shiraz, Iran. aaowji@yahoo.com
Khoshdel
Z
Z
Sanea
F
F
Panjehshahin
M R
MR
Shojaee Fard
M
M
Smith
D M
DM
Coppock
H A
HA
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000077270:Exenatide; D005934:Glucagon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010446:Peptide Fragments / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011498:Protein Precursors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014688:Venoms
D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D014688:Venoms; D012701:Serotonin; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide