Whole-Body Autoradiography of¹²³I-Labelled Islet Amyloid Polypeptide (IAPP) Accumulation in the lung parenchyma and in the villi of the intestinal mucosa in rats

Abstract

Islet amyloid polypeptide (IAPP) in a 37 amino-acid pancreatic islet polypeptide, displaying about 50% amino-acid homology with neuropeptide calcitonin gene-related peptide (CGRP). IAPP is co-stored with insulin in the beta-cell secretory granules and co-released with insulin upon stimulation. Human IAPP has the ability to precipitate in the shape of amyloid in patients with type II (non-insulin dependent) diabetes but otherwise its functional or pathophysiological role is enigmatic. In the present study 125I-labelled rat IAPP was injected i.v. into female Sprague-Dawley rats and the distribution of the peptide was examined by whole-body autoradiography at intervals from 2 to 30 min after administration. Already after 2 min high radioactivity occurred in the lung parenchyma and in the villi of the small intestinal mucosa. The high radioactivity in these tissues persisted at 10 min but at 30 min the radioactive labelling had decreased to a level only slightly higher than that observed in the blood. A high uptake of radioactivity was also seen in the cortex of the kidney. In other tissues, including the liver, the skeletal muscle, and the exocrine and endocrine pancreas, the radioactivity was low and did not exceed that of the blood. The uptake of 125I-IAPP in the lungs and in the small intestine was inhibited by simultaneous injections of either an excess of unlabelled rat IAPP or unlabelled rat CGRP. This indicates that the labelled structures observed in the lung and the small intestine after injection of 125I-IAPP alone was due to binding to receptors for IAPP or CGRP in these tissues. The accumulation of radioactivity in the kidneys was not affected by pretreatment with high doses of unlabelled IAPP or CGRP. This unspecific uptake of radioactivity may be due to reabsorption of labelled IAPP in the proximal tubuli. Our results indicate the presence of receptors binding IAPP in the lung parenchyma and in the villi of the small intestinal mucosa. This, in turn, may imply prominent biological activities of IAPP at these sites.

Characterization of transit rates in the large intestine of mice following treatment with a CGRP antibody, CGRP receptor antibody, and small molecule CGRP receptor antagonists

“…The uptake of amylin in lung and intestine was inhibited by administration of unlabeled amylin or CGRP. These results indicated that amylin was bound to receptors in these tissue, and likely exerted biological activity therein 39 . In rats, the intracerebroventricular (1–4 μg) or sc (25–100 μg/kg) administration dose‐dependently inhibited gastric emptying and intestinal transit of charcoal meal 20 .…”

“…Like CGRP, it is also expressed in many tissues in addition to the stomach and intestines, which include the lungs, peripheral nervous system, and the brain 20 . The iv injection of amylin radiolabeled with 125 I resulted in high levels of radioactivity in the lung parenchyma and in the villi of the small intestinal mucosa, and elevated levels in kidney cortical tissue, whereas radioactivity was low and remained similar to blood levels in other tissue 39 . The uptake of amylin in lung and intestine was inhibited by administration of unlabeled amylin or CGRP.…”

Amylin suppresses acetic acid-induced visceral pain and spinal c-fos expression in the mouse

“…Similar to CGRP receptors, amylin receptors are heterodimeric complex of calcitonin receptor (CTR) and receptor activity modifying proteins (RAMP) (Christopoulos et al, 1999). High affinity amylin binding sites are located in many regions of the rat and monkey brains; including the hypothalamus, nucleus accumbens, dorsal raphe and area postrema (Stridsberg et al, 1993; Sexton et al, 1994; Paxinos et al, 2004). Little is known relative to the function of amylin in the mammalian nervous system.…”