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Distribution of GLP‐1 Binding Sites in the Rat Brain: Evidence that Exendin‐4 is a Ligand of Brain GLP‐1 Binding Sites
Author(s) -
Göke Rüdiger,
Larsen Philip J.,
Mikkelsen Jens D.,
Sheikh Søren P.
Publication year - 1995
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1995.tb00650.x
Subject(s) - area postrema , subfornical organ , circumventricular organs , solitary tract , receptor , binding site , ligand (biochemistry) , biology , endocrinology , medicine , hypothalamus , nucleus , agonist , microbiology and biotechnology , chemistry , biochemistry , angiotensin ii
The distribution and biochemical properties of glucagon‐like peptide (GLP)‐1(7–36)amide (GLP‐1) binding sites in the rat brain were investigated. By receptor autoradiography of tissue sections, the highest densities of [ 125 I]GLP‐1 binding sites were identified in the lateral septum, the subfornical organ (SFO), the thalamus, the hypothalamus, the interpenduncular nucleus, the posterodorsal tegmental nucleus, the area postrema (AP), the inferior olive and the nucleus of the solitary tract (NTS). Binding studies with [ 125 I][Tyr39]exendin‐4, a GLP‐1 receptor agonist, showed an identical distribution pattern of binding sites. Binding specificity and affinity was investigated using sections of the brainstem containing the NTS. Binding of [ 125 I]GLP‐1 to the NTS was inhibited concentration‐dependently by unlabelled GLP‐1 and [Tyr39]exendin‐4 with K 1 values of 3.5 and 9.4 nM respectively. Cross‐linking of hypothalamic membranes with [ 125 I]GLP‐1 or [ 125 I][Tyr39]exendin‐4 identified a single ligand‐binding protein complex with a molecular mass of 63 000 Da. The fact that no GLP‐1 binding sites were detected in the cortex but that they were detected in the phylogenetically oldest parts of the brain emphasizes that GLP‐1 may be involved in the regulation of vital functions. In conclusion, the biochemical data support the idea that the central GLP‐1 receptor resembles the peripheral GLP‐1 receptor. Furthermore, the presence of GLP‐1 binding sites in the circumventricular organs suggests that these may be receptors which act as the target for both peripheral blood‐borne GLP‐1 and GLP‐1 in the nervous system.