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Endothelin binding and receptor down regulation in rat glomerular mesangial cells
1Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
The Journal of Pharmacology and Experimental Therapeutics
|February 1, 1991
Summary
This study found two types of endothelin (ET) binding sites on rat mesangial cells. ET receptor down-regulation affects cellular responses, impacting calcium signaling.
Area of Science:
- Pharmacology
- Cell Biology
- Renal Physiology
Background:
- Endothelin (ET) has diverse biological effects on mesangial cells, including proliferation and contraction.
- Understanding ET receptor subtypes is crucial for elucidating its role in renal function.
Purpose of the Study:
- To investigate the presence and characteristics of specific ET receptors on cultured rat mesangial cells.
- To determine the functional consequences of ET receptor modulation.
Main Methods:
- Radioligand binding assays using [125I]ET-1.
- Scatchard and heterologous competition analyses.
- Assessment of ET receptor down-regulation and intracellular calcium response.
Main Results:
- Rat mesangial cells possess high-affinity binding sites for ET-1 (Kd = 31.4 pM).
- Evidence suggests two binding sites for ET-related peptides, with distinct affinities for ET-3.
- ET-1 preincubation induced receptor down-regulation, reducing ET-1's effect on intracellular calcium.
Conclusions:
- Rat mesangial cells express at least two types of ET binding sites.
- ET receptor down-regulation has functional consequences on cellular signaling pathways.
- These findings contribute to understanding ET's role in mesangial cell biology.
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