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A pertussis toxin-sensitive GTP-binding protein couples endothelin to phospholipase C in rat mesangial cells
Journal article   Peer reviewed

A pertussis toxin-sensitive GTP-binding protein couples endothelin to phospholipase C in rat mesangial cells

Christie P Thomas, Mark Kester and M J Dunn
The American journal of physiology, Vol.260(3 Pt 2), pp.F347-F352
03/1991
DOI: 10.1152/ajprenal.1991.260.3.F347
PMID: 1900389

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Abstract

The mechanisms of stimulation of phospholipase C (PLC) by endothelin, specifically the role of guanine nucleotide-binding proteins (GTP-binding proteins) in coupling the endothelin receptor to PLC, were investigated in rat mesangial cells. Endothelin-1 (ET) synergistically released inositol polyphosphates in the presence of the stimulatory GTP analogue guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) in permeabilized cells. In addition, in intact cells, pertussis toxin partially inhibited the stimulation of total inositol phosphates (IPn) by ET. Pertussis toxin also reduced the peak ET-stimulated intracellular free calcium level ([Ca2+]i) in these cells, both in the presence and absence of extracellular calcium. Pertussis toxin induced ADP ribosylation of a 41- to 43-kDa protein in mesangial cell membranes, and this effect was inhibited by prior exposure to ET and augmented by the inhibitory GDP analogue, guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). Thus a pertussis toxin-sensitive GTP-binding protein is involved in the activation of PLC by ET in glomerular mesangial cells.
Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology Endothelins - pharmacology Inositol Phosphates - antagonists & inhibitors Calcium - metabolism Adenosine Diphosphate Ribose - metabolism Pertussis Toxin Rats Type C Phospholipases - metabolism Inositol Phosphates - pharmacology Virulence Factors, Bordetella - pharmacology Endothelins - metabolism Glomerular Mesangium - cytology Animals Glomerular Mesangium - metabolism GTP-Binding Proteins - metabolism

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