Identification and localization of glucagon-like peptide-1 and its receptor in rat brain.
The existence and distribution of glucagon-like peptide-1 (GLP-1) and its receptor in rat brain in relation to that of glucagon were examined. The concentration of GLP-1 immunoreactivity (GLP-1-IR), measured by a specific and sensitive RIA established in this study with anti GLP-1 serum (LMT-01), was found to be highest in the thalamus-hypothalamus, followed by the medulla oblongata. The distribution of glucagon-like immunoreactivity was similar to that of GLP-1-IR. However, appreciable glucagon immunoreactivity was detected only in the thalamus-hypothalamus. Gel filtration analysis showed the presence of GLP-1-IR of various molecular weights in the extract of thalamus-hypothalamus including that eluted at the same position as synthetic GLP-1 (1-37); moreover, HPLC analysis also confirmed the presence of GLP-1-IR, eluted at the exact position as synthetic GLP-1 (1-37). The distribution of receptors for GLP-1 corresponded with that of GLP-1-IR in the rat brain, except in the pituitary gland. The distribution of these receptors was also similar to that of glucagon receptors. The thalamus-hypothalamus, pituitary gland, and medulla oblongata were rich in GLP-1 and glucagon-binding sites. The binding affinities of GLP-1 and glucagon were in the nanomolar range [disocciation constant Kd approximately equal to 4 nM]. The presence of specific, high affinity receptors for GLP-1 was confirmed by demonstrating that GLP-1 stimulated cAMP formation in the thalamus-hypothalamus and the pituitary gland. The concentration of GLP-1 required for half-maximal stimulation of cAMP formation in these regions was about 1 nM. These results suggest that GLP-1 may be synthesized in certain parts of the brain and play a role as a neurosignal transmitter.
D000818:Animals; D001923:Brain Chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000096:biosynthesis; D005934:Glucagon / Q000032:analysis / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007031:Hypothalamus / Q000032:analysis; D008297:Male; D008526:Medulla Oblongata / Q000032:analysis; D010455:Peptides / Q000032:analysis* / Q000378:metabolism; D010902:Pituitary Gland / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000032:analysis / Q000378:metabolism; D018027:Receptors, Glucagon; D013788:Thalamus / Q000032:analysis; D014018:Tissue Distribution
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP