Skip to main content
SpringerLink
Log in

Differential distribution of endothelin peptides and receptors in human adrenal gland

  • Papers
  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

Sub-type selective ligands revealed a differential distribution of endothelin (ET) receptors within human adrenal glands. High densities of ETA receptors were localized, using [125I]-PD151242, to the smooth muscle layer of the arteries, smaller vessels within the capsular plexus and to the secretory cells of zona glomerulosa (K D=139.8±39.7,B max=69.7±9.1 fmol mg−1 protein, mean of 3 individuals±sem). ETB receptors were present in the medulla (K D=145.2±16.4,B max=75.5±12.3), zona glomerulosa (KD=100.6±35.1,B max=63.1±10.0), fasiculata (K D 145.1±162.,B max=67.9±6.9) and reticularis (KD=118.2±18.6,B max=71.9±6.5). ETB receptors were not detected within the smooth muscle of the vasculature. Messenger RNA encoding both sub-types was present in adrenals. ET-like immunoreactivity was localized to the cytoplasm of the endothelial cells from arteries supplying the gland and resistance vessels within the capsular plexus. Staining was also detected in these cells using anti-big ET-1 and less intensely with anti-big ET-2 antisera but not within cells within the cortex or medulla. Big ET-3-like immunoreactivity was localized to secretory cells of the medulla. Staining was not found using antiserum that could detect ET-3, suggesting further processing of big ET-3 may occur within the plasma, and that the cdrenals could be a source of ET-3. The presence of ET-1 was confirmed by high performance liquid chromatography and radioimmunoassay although ET-3 was not detected. The results suggest that ET-1 is the predominant mature isoform, which is localized mainly to adrenal vasculature, particularly the capsular plexus, and may contribute to blood flow regulation in the gland.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bacon, C. R., Morrison, J. J., O'Reilly, G., Cameron, I. T. &Davenport, A. P. ETA and ETB endothelin receptors in human myometrium characterized by the subtype selective ligands BQ123, BQ3020, FR139317 and PD151242.J. Endocrinol. 144, 127–34.

    CAS  PubMed  Google Scholar 

  • Boarddr, M. R. &Marriott, D. B. (1991) Endothelin-1 stimulation of noradrenaline and adrenaline release from adrenal chromaffin cells.Biochem. Pharmacol. 41, 521–6.

    Google Scholar 

  • Cameron, I. T., Plumpton, C., Champeney, R., Van Papendorp, C., Ashby, M. J. &Davenport, A. P. (1993) Identification of endothelin-1, endothelin-2 and endothelin-3 in human endometrium.J. Reproduction and Fertility 97, 251–5.

    Google Scholar 

  • Cozza, E. N., Gomez Sanchez, C. E., Foecking, M. F. &Chiou, S. (1989) Endothelin binding to cultured calf adrenal zona glomerulosa cells and stimulation of aldosterone secretion.J. Clin. Invest. 84, 1032–5.

    CAS  PubMed  Google Scholar 

  • Cyr, C., Huebner, K., Druck, T. &Kris, R. (1991) Cloning and chromosomal localization of a human endothelin ETA receptor.Biochem. Biophys. Res. Commun. 181, 184–90.

    Article  CAS  PubMed  Google Scholar 

  • Davenport, A. P. &Maguire, J. J. (1994) Is endothelin-induced vasoconstriction mediated only by ETA receptors in humans?Trends Pharm. Sci. 15, 9–11.

    CAS  PubMed  Google Scholar 

  • Davenport, A. P., Nunez, D. J., Hall, J. A., Kaumann, A. J. &Brown, M. J. (1989) Autoradiographical localization of binding sites for porcine (125I)endothelin-1 in humans, pigs, and rats: Functional relevance in humans.J. Cardiovasc. Pharmacol. 13 (5), S166–70.

    CAS  PubMed  Google Scholar 

  • Davenport, A. P., O'reilly, G., Molenaar, P., Maguire, J. J., Kuc, R. E., Sharkey, A., Bacon, C. R. &Ferro, A. (1993) Human endothelin receptors characterized using reverse transcriptase-polymerase chain reaction, in situ hybridization and sub-type selective ligands BQ123 and BQ3020: evidence for expression of ETB receptors in human vascular smooth muscle.J. Cardiovasc. Pharmacol. 22, S22–5.

    CAS  PubMed  Google Scholar 

  • Davenport, A. P., Kuc, R. E., Fitzgerald, F., Maguire, J. J., Berryman, K. &Doherty, A. M. (1994a) [125I]-PD151242: a selective radioligand for human ETA receptors.Br. J. Pharmacol. 111, 4–6.

    CAS  PubMed  Google Scholar 

  • Davenport, A. P., Kuc, R. E., Hoskins, S. L., Karet, F. E. &Fitzgerald, F. (1994b) [125I]-PD151242: a selective ligand for endothelin ETA receptors in human kidney which localises to renal vasculature.Br. J. Pharmacol. 113, 1303–10.

    CAS  PubMed  Google Scholar 

  • Davenport, A. P., O'reilly, G. &Kuc, R. E. (1995) Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA subtype.Br. J. Pharmacol. 114, 1110–16.

    CAS  PubMed  Google Scholar 

  • Gasic, S., Wagner, O. F., Vierhapper, H., Nowotny, P. &Waldhausl, W. (1992) Regional hemodynamic effects and clearance of endothelin-1 in humans: Renal and peripheral tissues may contribute to the overall disposal of the peptide.J. Cardiovasc. Pharmacol. 19, 176–80.

    CAS  PubMed  Google Scholar 

  • Hinson, J. P., Vinson, G. P., Kapas, S. &Teja, R. (1991) The role of endothelin in the control of adrenocortical function: stimulation of endothelin release by ACTH and the effects of endothelin-1 and endothelin-3 on steroidogenesis in rat and human adrenocortical cells.J. Endocrinol. 128, 275–80.

    CAS  PubMed  Google Scholar 

  • Hirata, Y., Imai, T., Eguchi, S. &Marumo, F. (1993) Concomitant expression of endothelin receptor subtype and isopeptide by pheochromocytoma and bovine adrenal medulla.Hyperten. Res. 16, 215–19.

    CAS  Google Scholar 

  • Howard, P. G., Plumption, C. &Davenport, A. P. 1992) Anatomical localization and pharmacological activity of mature endothelins and their precursors in human vascular tissue.J. Hyperten. 10, 1379–86.

    CAS  Google Scholar 

  • Imai, T., Hirata, Y., Eguchi, S., Kanno, K., Ohta, K., Emori, T., Sakamoto, A., Yanagisawa, M., Masaki, T. &Marumo, F. (1992) Concomitant expression of receptor subtype and isopeptide of endothelin by human adrenal gland.Biochem. Biophys. Res. Commun. 182, 1115–21.

    Article  CAS  PubMed  Google Scholar 

  • Karet, F. E. &Davenport, A. P. (1993) Human kidney: Endothelin isoforms detected by HPLC with radioimmunoassay and receptor subtypes detected using ligands BQ123 and BQ3020.J. Cardiovasc. Pharmacol. 22, S29–33.

    CAS  PubMed  Google Scholar 

  • Karet, F. E., Kuc, R. E. &Davenport, A. P. (1993) Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney.Kidney International 44, 36–42.

    CAS  PubMed  Google Scholar 

  • Karet, F. E., Charnockjones, D. S., Harrison-Woolrych, M. L. H., O'reilly, G., Davenport, A. P. &Smith, S. K. (1994) Quantification of mRNA in human tissue using fluorescent nested reverse-transcriptase polymerase chain reaction.Anal. Biochem. 220, 384–90.

    Article  CAS  PubMed  Google Scholar 

  • Kohzuki, M., Johnston, C. I., Chai, S. Y., Casley, D. J., Rogerson, F. &Mendelsohn, F. A. O. (1989) Endothelin receptors in rat adrenal gland visualized by quantitative autoradiography.Clin. Exp. Pharmacol. Physiol. 16, 239–42.

    CAS  PubMed  Google Scholar 

  • Maguire, J. J. &Davenport, A. P. (1995) ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.Br. J. Pharmacol. 115, 191–7.

    CAS  PubMed  Google Scholar 

  • Maguire, J. J., Kuc, R. E., O'reilly, G. &Davenport, A. P. (1994) Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro.Br. J. Pharmacol. 113, 49–54.

    CAS  PubMed  Google Scholar 

  • Marciniak, S. J., Plumpton, C., Barker, P. J., Huskisson N. S. &Davenport, A. P. (1992) Localization of immunoreactive endothelin and proendothelin in the human lung.Pulmon. Pharmacol. 5, 175–82.

    CAS  Google Scholar 

  • Molenaar, P., Kuc, R. E. &Davenport, A. P. (1992) Characterisation of two new ETB selective radioligands, [125I]-BQ3020 and [125I]-[Ala1, 3, 11, 15JET-1 in human heart.Br. J. Pharmacol. 107, 637–9.

    CAS  PubMed  Google Scholar 

  • Molenaar, P., O'reilly, G., Sharkey, A., Kuc, R. E., Harding, D. P., Plumpton, C., Gresham, G. A., &Davenport, A. P. (1993) Characterisation and localization of endothelin receptor sub-types in the human atrioventricular conducting system and myocardium.Circ. Res. 72, 526–38.

    CAS  PubMed  Google Scholar 

  • Nakao, K., Arai, H., Hosoda, K., Ogawa, Y., Nakagawa, O., Suga, S. I., Nakanishi, S. &Imura, H. (1991) Molecular cloning of two subtypes of human endothelin receptor.J. Vasc. Med. Biol. 3, 303–7.

    Google Scholar 

  • Naruse, M., Fujimaki, Y., Naruse, K., Yoshimoto, T., Kawai, M., Tanabe, A., Tanaka, M., Imaki, T., Shibasaki, T., Ito, Y., Obara, T., Hagiwara, H., Hirose, S., Yano, M., Demura, R., &Demura, H. (1995) Pathophysiological role of endothelin in adrenal gland: A local modulator of aldosterone secretion. InEndocrinology: New Advances (edited byBaldi, E., Maggi, M., Cameron, I. T. &Dunn, M. J.), pp. 241–53. Rome: Ares Serono Symposia.

    Google Scholar 

  • O'Reilly, G., Charnock-Jones, D. S., Davenport, A. P., Cameron, I. T. &Smith, S. K. (1992) Presence of mRNA for endothelin-1, endothelin-2, and endothelin-3 in human endometrium, and a change in the ratio of ETA and ETB receptor subtype across the menstrual cycle.J. Clin. Endocrin. Metabolism. 75, 1545–9.

    Google Scholar 

  • Peter, M. G. &Davenport, A. P. (1995) Selectivity of (125I)-PD151242 for human, rat and porcine endothelin ETA receptors in the heart.Br. J. Pharmacol. 114, 297–302.

    CAS  PubMed  Google Scholar 

  • Pierre, L. N. &Davenport, A. P. (1995) Autoradiographic study of endothelin receptors in human cerebral arteries.J. Cardiovasc. Pharmacol.,26, S326–8.

    CAS  PubMed  Google Scholar 

  • Plumpton, C., Champeney, R., Ashby, M. J., Kuc, R. E. &Davenport, A. P. (1993) Characterization of endothelin isoforms in human heart: Endothelin-2 demonstrated.J. Cardiovasc. Pharmacol. 22, S26–8.

    CAS  PubMed  Google Scholar 

  • Plumpton, C., Haynes, W. G., Webb, D. J. &Davenport, A. P. (1995) Phosphoramidon inhibition of the in vivo conversion of big endothelin-1 to endothelin-1 in the human forearm.Br. J. Pharmacol. 115, 1821–8.

    Google Scholar 

  • Plumpton, C., Ashby, M. J., Kuc, R. E., O'reilly, G. &Davenport, A. P. (1996) Expression of endothelin peptides and mRNA in the human heart.Clin. Sci. 89, 37–46.

    Google Scholar 

  • Rossi, G., Albertin, G., Belloni, A., Zanin, L., Biasolo, M. A., Prayergaletti, T., Bader, M., Nussdorfer, G. G., Palu, G. &Pessina, A. C. (1994) Gene expression, localization, and characterization of endothelin A and B receptors in the human adrenal cortex.J. Clin. Invest. 94, 1226–34.

    CAS  PubMed  Google Scholar 

  • Suzuki, N., Matsumoto, H., Miyauchi, T., Goto, K., Masaki, T., Tsuda, M. &Fujino, M. (1990). Endothelin-3 concentrations in human plasma: the increased concentrations in patients undergoing haemodialysis.Biochem. Biophys. Res. Commun. 169, 809–15.

    Article  CAS  PubMed  Google Scholar 

  • Vierhapper, H., Wagner, O., Nowotny, P. &Waldhausl, W. (1990) Effect of endothelin-1 in man.Circulation 81, 1415–18.

    CAS  PubMed  Google Scholar 

  • Vierhapper, H., Nowotny, P. &Waldhausl, W. (1995) Effect of endothelin-1 in man: Impact on basal adrenocorticotropin-stimulated concentrations of aldosterone.J. Clin. Endocrinol. Metab. 80, 948–51.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, Level 2, F and G Block, CB2 2QQ, Cambridge, UK

    A. P. Davenport, S. L. Hoskins, R. E. Kuc & C. Plumpton

Authors
  1. A. P. Davenport
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. L. Hoskins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. E. Kuc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Plumpton
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davenport, A.P., Hoskins, S.L., Kuc, R.E. et al. Differential distribution of endothelin peptides and receptors in human adrenal gland. Histochem J 28, 779–789 (1996). https://doi.org/10.1007/BF02272151

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02272151

Keywords

Search

Navigation