M. Sokolovsky, FUNCTIONAL COUPLING BETWEEN ENDOTHELIN RECEPTORS AND MULTIPLE G-PROTEINS IN RAT-HEART MYOCYTES, Receptors & channels, 1(4), 1993, pp. 295-304
Binding data point to the coexistence of three endothelin receptors (E
T-R) in rat heart myocytes. Induction of phosphoinositide hydrolysis i
n this preparation by endothelins (ET-1 and ET-3) or sarafotoxins (SRT
X-b and SRTX-c) was demonstrated by measurement of labeled inositol ph
osphate generation. Pertussis toxin (PT) enhanced the induction of pho
sphoinositide hydrolysis by all four peptides. The process seems to be
mediated by at least two heterotrimeric G-proteins, the one sensitive
and the other insensitive to PT. Measurement of GTPase activity induc
ed in rat myocytes clearly indicates for the first time the direct fun
ctional coupling between ET-R and a G-protein. These GTPase activity e
xperiments provide evidence that phosphoinositide hydrolysis is stimul
ated via functional coupling between the endothelin receptor of the ET
(A)-R subtype and a PT-insensitive G-protein, Gq/11. The involvement o
f PT-sensitive G-proteins, i.e. Gi-like and/or Go-like proteins, in th
e signal transduction pathways of ETs and SRTXs is discussed.