AUTORADIOGRAPHIC DISTRIBUTION AND RECEPTOR-BINDING PROFILE OF [I-125]BOLTON HUNTER-RAT AMYLIN BINDING-SITES IN THE RAT-BRAIN

Amylin is a recently isolated peptide from amyloid plaques in noninsul in-dependent diabetic patients and showed high sequence homology with calcitonin gene-related peptide. We investigated the distribution and the binding profile of [I-125]Bolton Hunter-rat amylin ([I-125]BH-rat amylin) binding sites in the rat brain, as well as the affinity of rat amylin for [I-125]hCGRP alpha binding sites in the brain, atrium (CGR P, receptor-enriched tissue) and vas deferens (CGRP(2) receptor-enrich ed tissue). High amounts of high affinity [I-125]BH-rat amylin binding sites were observed in the nucleus accumbens, various hypothalamic nu clei, amygdaloid body, dorsal raphe, tegmental and parabrachial nuclei and the locus ceruleus. Interestingly, both rat amylin and salmon cal citonin revealed low nanomolar affinities (2-19 nM) for [I-125]BH-rat amylin binding sites in the Various brain areas, whereas human calcito nin gene-related peptide-alpha (hCGRP alpha) showed lower affinities r anging between 13 to 150 nM. Moreover, the affinity of rat amylin was much lower than that of hCGRP alpha for [I-125]hCGRP alpha binding in the brain, atrium and vas deferens, except for very few areas such as the nucleus accumbens and ventral striatum. Similarly, rat amylin was much weaker (100- to 400-fold) than hCGRP alpha to induce a biological effect in the atrium and vas deferens. These results thus suggest the existence of unique [I-125]BH-rat amylin binding sites in the rat bra in as well as limited cross-reactivity between rat amylin and [I-125]h CGRP alpha receptors present in the brain, atrium and vas deferens.