Amylin binding in rat renal cortex, stimulation of adenylyl cyclase, and activation of plasma renin

Abstract

125I-labeled rat amylin binds to specific sites in the cortex of rat kidney, which can be distinguished from those for 125I-labeled salmon calcitonin (sCT) and 125I-labeled rat alpha-calcitonin gene-related peptide (alpha-CGRP) on the basis of regional distribution. These sites have a high affinity (approximately 1 nM) for amylin, and 125I-amylin binding is potently inhibited by the peptide antagonists AC413 and sCT-(8-32), whereas CGRP-(8-37) is a poor inhibitor of binding. Furthermore, incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibits 125I-amylin binding by > 90%, indicating that binding is dependent on coupling to G proteins. In renal cortex, amylin stimulated adenylyl cyclase activity three- to fourfold, and this was inhibited by AC413 and sCT-(8-32) but not by CGRP-(8-37). Amylin activated plasma renin twofold, and this was blunted by prior administration of AC413 but not CGRP-(8-37). We speculate that amylin may play an important role in renal physiology and that in states of hyperamylinemia, as found in obesity and the insulin resistance syndrome, this peptide may be involved in the genesis and development of hypertension.

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

“…In brief, in situ autoradiographic images were placed on a uniformly illuminating fluorescent light box (Northern Light Precision Luminator Model C60, Image Research, Ontario, Canada) and captured using a video camera (Sony Video Camera Module CCD, Tokyo, Japan) connected to an IBM AT computer with a 512 512 pixel array imaging board with 256 grey levels. After appropriate calibration by constructing a curve of optical density and radioactivity [24,25] quantification of digitalized autoradiographic images was done using MCID software. Data were expressed as the ratio [in arbitray units (AU)] of the optical density (OD) relative to control retinae which were assigned a value of 1.…”

Increased epidermal growth factor in experimental diabetes related kidney growth in rats

“…In brief, in situ autoradiographic images were placed on a uniformly illuminating fluorescent light box (Northern Light Precision Luminator Model C60; Image Research, Ontario, Canada) and captured using a video camera (Sony Video Camera Module CCD, Tokyo, Japan) connected to an IBM AT computer with a 512 × 512 pixel array imaging board with 256 gray levels. Following appropriate calibration by constructing a calibration curve of optical density versus radioactivity [21,22] quantitation of digitalized autoradiographic images was performed with the MCID software and expressed as relative optical density (ROD). Cortex:outer medulla ROD was analysed in control and day 7 diabetic animals.…”

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

“…Amylin contributes to the perception of satiety and may have a site of action within the central nervous system [58]. It has binding sites within the renal cortex [54,59], where it promotes renin secretion [59,60]. Amylin is cosynthesized, copackaged, and cosecreted in the insulin secretory granule of the β cell and parallels insulin secretion [4].…”