IN-VITRO AUTORADIOGRAPHIC LOCALIZATION OF AMYLIN BINDING-SITES IN RAT-BRAIN

Amylin is a recently discovered 37 amino acid peptide which is co-secr eted from the pancreas with insulin and acts to modulate carbohydrate metabolism Recently, high-affinity binding sites for [I-125]rat amylin have been identified in the rat central nervous system. These sites a lso have high affinity for the structurally related peptides calcitoni n gene-related peptide and salmon calcitonin. In the present study we have used in vitro autoradiography to map the distribution of these [I -125]rat amylin binding sites in rat brain. High to moderate levels of binding were present in mid-caudal accumbens nucleus, fundus striati and parts of the bed nucleus of the stria terminalis and substantia in ominata. This binding extended caudally into parts of the amygdalostri atal transition zone and the central and medial amygdaloid nuclei. Hig h to moderate levels of binding also occurred in much of the hypothala mus including the medial preoptic, dorsomedial hypothalamic and medial tuberal nuclei as well as the ventrolateral subnucleus of the ventrom edial hypothalamic nucleus. Other regions of high level binding includ ed the subfornical organ, the vascular organ of the lamina terminalis, area postrema, locus coeruleus, dorsal raphe and caudal parts of the nucleus of the solitary tract. The subfornical organ, vascular organ o f the lamina terminalis and area postrema, which display some of the h ighest binding densities, lack a patent blood-brain barrier and thus c ould be responsive to blood-borne amylin. In conclusion we have mapped , in detail, the distribution of amylin binding sites in rat brain. Th e location of binding is consistent with potential roles for these sit es in appetite, fluid and electrolyte homeostasis, autonomic function and regulation of mood.