HIGH-AFFINITY AMYLIN BINDING-SITES IN RAT-BRAIN

Amylin, a 37-amino acid peptide structurally related to calcitonin gen e-related peptide, is synthesized in and released along with insulin f rom pancreatic beta-cells. Amylin is proposed to act as an endocrine p artner to insulin, in part through actions upon skeletal muscle that p romote cycling of gluconeogenic precursors to liver. We report here th at binding sites with high affinity (K(d) = 27 pm) for radioiodinated rat amylin are present in the nucleus accumbens region of rat brain. C ompetition experiments show that sites measured in nucleus accumbens m embranes have high affinity for rat amylin, lower affinity for rat cal citonin gene-related peptides, and very low affinity for rat calcitoni n. In contrast to rat calcitonin, salmon calcitonin has a high affinit y for these sites, indicating that it shares critical binding determin ants with amylin. We further tested whether salmon calcitonin shares w ith amylin the ability to regulate glycogen metabolism in rat skeletal muscle. Salmon calcitonin potently inhibits insulin-stimulated glucos e incorporation into rat soleus muscle glycogen, suggesting that rat s keletal muscle may also contain receptor populations that have high af finity for both amylin and salmon calcitonin.