GLUCAGON-LIKE PEPTIDE-I RECEPTORS IN THE SUBFORNICAL ORGAN AND THE AREA POSTREMA ARE ACCESSIBLE TO CIRCULATING GLUCAGON-LIKE PEPTIDE-I

The intestinal incretin hormone glucagon-like peptide I (GLP-I) inhibi ts gastric motility and secretion in normal, but not in vagotomized su bjects, pointing to a centrally mediated effect. Therefore, our aim wa s to study the availability of rat brain GLP-I receptors to peripheral ly injected I-125-labeled GLP-I. The specificity of the binding was te sted by co-injection of excess amounts of unlabeled GLP-I, Using light microscopical autoradiography of rat brain sections, we found specifi c I-125-GLP-I binding exclusively in the subfornical organ and the are a postrema, This binding was abolished when an excess amount of unlabe led GLP-I was co-injected with the labeled GLP-I, We conclude that cel ls in the subfornical organ and the area postrema could be responsive to blood-borne GLP-I, The observed binding of peripherally administere d GLP-I to the subfornical organ and the area postrema, which both hav e close neuroanatomical connections with hypothalamic areas involved i n water and appetite homeostasis, is consistent with the potential rol es of circulating GLP-I in the central regulation of appetite and auto nomic functions.