Natriuretic peptides receptors in human aldosterone-secreting adenomas.
Atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP) inhibit aldosterone secretion in humans both in vitro and in vivo. Unresponsiveness of aldosterone-secreting adenomas (aldosteronomas) to ANP in vitro and in vivo, might be due to reduced expression of the biologically-active natriuretic peptide receptor type A (NPr-A) and/or increased expression of the clearance receptor for natriuretic peptides (NPr-C). Therefore, we have analyzed NPr gene expression and ANP binding sites in human adrenals and aldosteronomas. Using reverse transcription and polymerase chain reaction, we cloned and characterized cDNAs for NPr-A, NPr-C, and the receptor (NPr-B) for the C-type natriuretic peptide (CNP). Total RNA from three normal human adrenals (obtained at surgery from patients with renal cancer) and five aldosteronomas were used for Northern analysis. NPr-A mRNA (approximately 4 kb) and NPr-B mRNA (approximately 4 kb) were expressed without significant differences in adrenals and in aldosteronomas except in an aldosteronomas that contained only very low amounts of NPr mRNAs. The gene expression of NPr-C was barely detectable both in adrenals and in aldosteronomas. ANP binding sites were analyzed by autoradiography with 125I-labeled ligand in other six aldosteronomas. Only one of the adenomas analyzed showed ANP binding sites with density of granules similar to nonadenomatous glomerulosa, whereas the others had significantly reduced densities. In summary, aldosteronomas express the genes encoding for NPr but mainly NPr-A, similarly to control adrenals. On the contrary, the binding sites for ANP are greatly reduced in most aldosteronomas. A somatic mutation or a post-transcriptional defect that reduces ANP binding sites might be present in some aldosteronomas.
Sarzani
R
R
Istituto di Medicina Clinica, University of Ancona, Italy.
Opocher
G
G
Paci
M V
MV
Belloni
A S
AS
Mantero
F
F
Dessì-Fulgheri
P
P
Rappelli
A
A
D000236:Adenoma / Q000737:chemistry / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000737:chemistry / Q000378:metabolism*; D000311:Adrenal Glands / Q000737:chemistry / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001345:Autoradiography; D015152:Blotting, Northern; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; C058930:brain natriuretic peptide receptor; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C