Islet amyloid polypeptide (IAPP) competes for two binding sites of CGRP.
Two distinct binding sites for [125I]human calcitonin gene-related peptide (hCGRP) were found in rat brain, skeletal muscle, and liver. Each tissue had a high affinity site with an average Kd of 46 pM and a low affinity site with an average Kd of 22 nM. Islet amyloid polypeptide (IAPP), which has N- and C-terminal sequence homology to CGRP and is produced by islet beta-cells, bound to both sites but had a potency closer to that of CGRP at the low affinity binding site. A C-terminal fragment of IAPP competed for [125I]hCGRP binding at the low affinity site with potency comparable to that of hIAPP. No specific binding to membrane preparations was found in experiments using [125I]rIAPP, which was iodinated at the C-terminal tyrosyl residue. These results suggest that some of the previously reported biological effects occurring at nM or microM concentrations of IAPP may be mediated by IAPP binding to low affinity CGRP receptors. This study further indicates that the C-terminal region of IAPP is important for binding to low affinity CGRP receptors, and suggests that C-terminal fragments of IAPP may be of biological importance.
Galeazza
M T
MT
Graduate Program in Neuroscience, University of Minnesota, Minneapolis.
O'Brien
T D
TD
Johnson
K H
KH
Seybold
V S
VS
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D015740:Calcitonin Gene-Related Peptide