AJP - Renal Physiology, Vol 260, Issue 3 347-F352, Copyright © 1991 by American Physiological Society
A pertussis toxin-sensitive GTP-binding protein couples endothelin to phospholipase C in rat mesangial cells
C. P. Thomas, M. Kester and M. J. Dunn
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
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.
