Expression and function of adrenomedullin and its receptors in Conn's adenoma cells

  • Authors:
    • Myriam Forneris
    • Lucia Gottardo
    • Giovanna Albertin
    • Ludwik K. Malendowicz
    • Gastone G. Nussdorfer
  • View Affiliations

  • Published online on: December 1, 2001     https://doi.org/10.3892/ijmm.8.6.675
  • Pages: 675-679
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Abstract

Adrenomedullin (ADM) is a hypotensive peptide, that derives from the proteolytic cleavage of pro(p)ADM and acts through two subtypes of receptors, called L1-receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR may function as a calcitonin gene-related peptide or a selective ADM receptor depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of proteins, named receptor-activity modifying proteins (RAMPs). Reverse transcription (RT)-polymerase chain reaction (PCR) allowed the detection of pADM mRNA in dispersed cells of eight Conn's adenomas (aldosteronomas). These cells also expressed peptidyl-glycine α-amidating monooxigenase, the enzyme converting immature ADM to the mature form, and contained sizeable amounts of ADM-immunoreactivity as measured by radioimmunoassay. RT-PCR also demonstrated the presence in aldosteronoma cells of the specific mRNAs of L1-R, CRLR and RAMPs 1-3. ADM (10-8 M) inhibited angiotensin-II (10-9 M)-simulated aldosterone secretion from cultured aldosteronoma cells, without affecting basal production. ADM (10-8 M) also enhanced basal proliferation rate of cultured cells, as estimated by the 5-bromo-2'-deoxyuridine immunocytochemical technique. Both effects of ADM were annulled by the ADM-receptor selective antagonist ADM22-52 (10-7 M). In conclusion, our study provides evidence that aldosteronoma cells express both ADM and ADM22-52-sensitive receptors. These findings, coupled with the demonstration that ADM exerts an aldosterone antisecretagogue action and a proliferogenic effect on cultured aldosteronoma cells, make it likely that endogenous ADM system plays a potentially important role in the paracrine or autocrine functional control of Conn's adenomas.

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December 2001
Volume 8 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Forneris, M., Gottardo, L., Albertin, G., Malendowicz, L.K., & Nussdorfer, G.G. (2001). Expression and function of adrenomedullin and its receptors in Conn's adenoma cells. International Journal of Molecular Medicine, 8, 675-679. https://doi.org/10.3892/ijmm.8.6.675
MLA
Forneris, M., Gottardo, L., Albertin, G., Malendowicz, L. K., Nussdorfer, G. G."Expression and function of adrenomedullin and its receptors in Conn's adenoma cells". International Journal of Molecular Medicine 8.6 (2001): 675-679.
Chicago
Forneris, M., Gottardo, L., Albertin, G., Malendowicz, L. K., Nussdorfer, G. G."Expression and function of adrenomedullin and its receptors in Conn's adenoma cells". International Journal of Molecular Medicine 8, no. 6 (2001): 675-679. https://doi.org/10.3892/ijmm.8.6.675