Selective release of glutamine and glutamic acid produced by perfusion of GLP-1 (7-36) amide in the basal ganglia of the conscious rat.

Glucagon-like peptide 1 (GLP-1)(7-36) amide, a member of the family of glucagon and related peptides, synthesized by intestinal L cells, has a well-defined distribution in rat brain. In addition, specific GLP-1(7-36) amide receptors have also been localized in some regions of the brain, which suggests that this novel gut-brain peptide has a role in brain function. Accordingly, we investigated the effects of this peptide on the release of amino acid neurotransmitters in the basal ganglia of conscious rats after its perfusion through a concentric "push-pull" cannula system with an artificial cerebrospinal fluid. To obtain stable basal levels of amino acids, the basal ganglia were perfused with an artificial cerebrospinal fluid for 2 h at a flow rate of 20 microliters/min and then with GLP-1(7-36) amide for 10 min, followed by 40 min poststimulation perfusion. GLP-1(7-36) amide produced an immediate increase (p less than 0.01) of the extracellular levels of glutamine and glutamic acid in the basal ganglia. By contrast, this peptide has no effect on the levels of aspartic acid, glycine, and serine. Because glutamine is a metabolic precursor of glutamic acid and is synthesized almost exclusively in astrocytes, these findings suggest a stimulatory effect of GLP-1(7-36) amide on astrocytes and/or neurons of the rat basal ganglia.