Endothelin receptors and coupled GTP-binding proteins in glomerular mesangial cells

Christie P Thomas; Elisabetta Baldi; Michael S Simonson; Mark Kester; Michael J Dunn

doi:10.1097/00005344-199100177-00022

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Endothelin receptors and coupled GTP-binding proteins in glomerular mesangial cells

Journal article

Peer reviewed

Endothelin receptors and coupled GTP-binding proteins in glomerular mesangial cells

Christie P Thomas, Elisabetta Baldi, Michael S Simonson, Mark Kester and Michael J Dunn

Journal of cardiovascular pharmacology, Vol.17 Suppl 7(7), pp.S79-S79

1991

DOI: 10.1097/00005344-199100177-00022

PMID: 1725439

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Abstract

Endothelins (ETs) are a family of vasoactive peptides with profound biological actions in diverse cell systems. Among its varied actions, ET stimulates phospholipase C (PLC) in cultured mesangial cells. We investigated the presence of specific ET receptors in rat mesangial cells in culture, and studied the role of GTP-binding proteins (G proteins) in coupling PLC to the endothelin receptor. [125I]ET binding was time- and temperature-dependent, and Scatchard analysis of saturation data showed a single class of high-affinity binding sites. Heterologous displacement with two related peptides, ET-3 and sarafotoxin (SFTX), revealed the presence of two binding sites for these isopeptides. Preincubation of cells with ET-1 reduced the receptor number without affecting Kd, and this effect was not prevented by protein kinase C inhibition or downregulation. We confirmed the presence of a 41- to 43-kDa pertussis toxin substrate in rat mesangial cell membranes in an ADP ribosylation assay. ET-1 inhibits and GDP beta S enhances toxin-catalyzed transfer of ADP-ribose to this substrate. ET-1 potentiated GTP gamma S-induced phosphatidylinositol (PI) hydrolysis in a concentration-dependent manner. In addition, pertussis toxin partially inhibited ET-stimulated PI hydrolysis in intact mesangial cells. Pertussis toxin also reduced the magnitude of ET-stimulated intracellular free calcium [( Ca2+ )i]. Thus, ET-1 binds to specific receptors on rat mesangial cells and activates PLC, in part, through a pertussis toxin-sensitive G-protein.

Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology

Temperature

Endothelins - pharmacology

Adenosine Diphosphate Ribose - metabolism

Pertussis Toxin

Rats

Receptors, Cell Surface - metabolism

Type C Phospholipases - metabolism

Virulence Factors, Bordetella - pharmacology

Endothelins - metabolism

Rats, Inbred Strains

Glomerular Mesangium - enzymology

Type C Phospholipases - antagonists & inhibitors

Receptors, Endothelin

Animals

Glomerular Mesangium - metabolism

Fura-2

Kinetics

In Vitro Techniques

Enzyme Activation - physiology

GTP-Binding Proteins - metabolism

Details

Title: Subtitle: Endothelin receptors and coupled GTP-binding proteins in glomerular mesangial cells
Creators: Christie P Thomas - Department of Medicine, Case Western Reserve University, Cleveland, Ohio
Elisabetta Baldi
Michael S Simonson
Mark Kester
Michael J Dunn
Resource Type: Journal article
Publication Details: Journal of cardiovascular pharmacology, Vol.17 Suppl 7(7), pp.S79-S79
Publisher: United States
DOI: 10.1097/00005344-199100177-00022
PMID: 1725439
ISSN: 0160-2446
eISSN: 1533-4023
Grant note: HL-37117 / NHLBI NIH HHS HL-22563 / NHLBI NIH HHS
Language: English
Date published: 1991
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Nephrology; Internal Medicine
Record Identifier: 9983986367602771

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