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Endothelin receptor in benign prostatic hyperplastic cells. Binding and functional studies

J R Wu-Wong1, W J Chiou, B Saeed

  • 1Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.

Receptors & Signal Transduction
|January 1, 1997
PubMed
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Endothelin receptors, specifically ET(A), are present in benign prostatic hyperplasia cells. ET-1 binding and functional effects are mediated by ET(A) receptors, suggesting a role in benign prostatic hyperplasia.

Area of Science:

  • Endocrinology
  • Urology
  • Molecular Biology

Background:

  • Endothelins (ETs) are vasoactive peptides with diverse physiological roles.
  • Benign prostatic hyperplasia (BPH) is a common condition in aging men.
  • The role of endothelins in BPH pathophysiology is not fully understood.

Purpose of the Study:

  • To characterize endothelin receptors in benign prostatic hyperplasia-1 (BPH-1) cells.
  • To investigate the functional effects of endothelin-1 (ET-1) in BPH-1 cells.
  • To determine the specific endothelin receptor subtype mediating these effects.

Main Methods:

  • Radioligand binding assays using [(125)I]ET-1 and [(125)I]ET-3.
  • Competitive binding studies with various endothelin receptor antagonists.

Related Experiment Videos

  • Reverse transcription-polymerase chain reaction (RT-PCR) for receptor expression analysis.
  • Measurement of intracellular calcium (Ca2+) concentrations and phosphatidylinositol hydrolysis.

    • Main Results:

    • BPH-1 cells exhibit high-affinity binding for ET-1 and ET-3.
    • RT-PCR confirmed higher expression of ET(A) receptors compared to ET(B) receptors.
    • ET-1 induced modest phosphatidylinositol hydrolysis and a significant increase in intracellular Ca2+.
    • ET(A)-selective antagonists completely blocked the functional effects of ET-1.

    Conclusions:

    • Benign prostatic hyperplasia cells express functional ET(A) receptors.
    • Endothelin signaling, primarily via ET(A) receptors, may play a significant role in benign prostatic hyperplasia.
    • Targeting endothelin receptors could be a potential therapeutic strategy for BPH.