High affinity amylin binding sites in rat brain.
Amylin, a 37-amino acid peptide structurally related to calcitonin gene-related peptide, is synthesized in and released along with insulin from pancreatic beta-cells. Amylin is proposed to act as an endocrine partner to insulin, in part through actions upon skeletal muscle that promote cycling of gluconeogenic precursors to liver. We report here that binding sites with high affinity (Kd = 27 pm) for radioiodinated rat amylin are present in the nucleus accumbens region of rat brain. Competition experiments show that sites measured in nucleus accumbens membranes have high affinity for rat amylin, lower affinity for rat calcitonin gene-related peptides, and very low affinity for rat calcitonin. In contrast to rat calcitonin, salmon calcitonin has a high affinity for these sites, indicating that it shares critical binding determinants with amylin. We further tested whether salmon calcitonin shares with amylin the ability to regulate glycogen metabolism in rat skeletal muscle. Salmon calcitonin potently inhibits insulin-stimulated glucose incorporation into rat soleus muscle glycogen, suggesting that rat skeletal muscle may also contain receptor populations that have high affinity for both amylin and salmon calcitonin.
Beaumont
K
K
Amylin Pharmaceuticals, Inc., San Diego, California 92121.
Kenney
M A
MA
Young
A A
AA
Rink
T J
TJ
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D013388:Succinimides
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D011956:Receptors, Cell Surface; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D013388:Succinimides; C022581:Bolton-Hunter reagent; C028815:salmon calcitonin; D006003:Glycogen; D002116:Calcitonin