Internalization of atrial natriuretic peptide by adrenal glomerulosa cells

Abstract

Internalization of 125I-labelled atrial natriuretic peptide ([ 125I]ANP) by rat adrenal glomerulosa cells in vivo was investigated by means of an ultrastructural autoradiographic approach. One to 30 min after IV injection of [125I]ANP, silver grains were found, at the light microscope level, over all glomerulosa cells; coinjection of 20 micrograms of unlabelled ANP inhibited this binding by 64%. At the electron microscope level, the time-course study indicated maximal silver grain densities in plasma membranes 1 min after IV injection; grains were detected in mitochondria (external membranes and matrix) 2 min after injection, with maximal labelling at 15 min. The cytoplasmic matrix was labelled only 30 min after injection. During the time-course, labelling of nuclei, Golgi apparatus, and lysosomes was minimal. The data suggest that after binding to plasma membranes ANP is rapidly internalized and distributed within glomerulosa cells. The association of radioactivity with mitochondria suggests that ANP may have intracellular sites of action complementary to those on plasma membranes.

Regulation of mitochondria function by natriuretic peptides

“…ANP is an intracrine signaling molecule, and adrenal cortical cells are among the target cells that have been shown to internalize it. High-affinity binding sites for ANP have been identified on adrenal mitochondrial membranes, and intracellular ANP has been found in association with mitochondria (18,30,31). Interestingly, the published data are very sparse as to the regulation of mitochondria function by NPs in the kidney.…”

Atrial natriuretic peptide signaling co-regulates lipid metabolism and ventricular conduction system gene expression in the embryonic heart

“…Indeed, ANP was shown to bind directly to the mitochondrial membrane in rat adrenocortical cells. 51 , 52 It is not known whether mitochondrial membranes in adrenocortical cells or E11.5 ventricular cells harbor NPRA like binding sites and whether A7 can also bind to such sites. Differential binding of ANP vs. A7 at such intracellular vs. extracellular target sites may explain the unexpected results observed with ANP+A7 co-treatments in this study.…”

The mitochondrial component of intracrine action

“…ANP is also an intracrine, and adrenal cortical cells are among those target cells that have been shown to internalize it. High-affinity binding sites for ANP have been identified on adrenal mitochondrial membranes, and intracellular ANP has been found in association with mitochondria (25,36,37). Other studies have shown that the direct application of recombinant ANP to renal mitochondria inhibited step 3 mitochondrial respiration and decreased the ADP-to-oxygen ratio; low molecular weight ANP also induced marked mitochondrial swelling (29).…”