Distribution of GLP‐1 Binding Sites in the Rat Brain: Evidence that Exendin‐4 is a Ligand of Brain GLP‐1 Binding Sites

European Journal of Neuroscience - Tập 7 Số 11 - Trang 2294-2300 - 1995
Rüdiger Göke1, Philip J. Larsen2, Jens D. Mikkelsen2, Søren P. Sheikh1
1Laboratory of Clinical Pharmacology, Department of Clinical Biochemistry, Rigshospitalet 7642
2Institute of Medical Anatomy B, University of Copenhagen, Denmark

Tóm tắt

AbstractThe 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 [125I]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 [125I][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 [125I]GLP‐1 to the NTS was inhibited concentration‐dependently by unlabelled GLP‐1 and [Tyr39]exendin‐4 with K1 values of 3.5 and 9.4 nM respectively. Cross‐linking of hypothalamic membranes with [125I]GLP‐1 or [125I][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.

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European Journal of Neuroscience

Tập 7 Số 11

2294-2300

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