Cl. Cioffi et M. Garay, SHORT-TERM REGULATION OF ENDOTHELIN RECEPTOR-MEDIATED PHOSPHOINOSITIDE HYDROLYSIS AND ARACHIDONIC-ACID RELEASE IN A7R5 SMOOTH-MUSCLE CELLS, Journal of cardiovascular pharmacology, 22, 1993, pp. 190000168-190000170
In this study, the short-term regulation of endothelin-1- (ET-1) induc
ed phosphoinositide (PI) hydrolysis and arachidonic acid release were
investigated in cultured rat aortic smooth-muscle cells. ET-1, but not
the ETB-selective peptide sarafotoxin (SFX) S6c, induced a dose-depen
dent increase in [H-3]inositol phosphate release (EC50 = 0.4 +/- 0.1 n
M). ET-3 stimulated this response only at concentrations >0.1 muM. The
ETA receptor antagonist BQ-123 inhibited ET-1-induced PI turnover, wi
th an IC50 value of 97 +/- 15 nM. Pre-exposure of intact cells to ET-1
resulted in a 72% and 73% reduction in the ability of ET-1 or SFX S6b
, respectively, to stimulate [H-3]inositol phosphate release, without
affecting the response to vasopressin. In contrast, PI turnover induce
d by ET-1 or SFX S6b was only slightly lowered, by 28% and 22%, after
a 30-min preincubation period with SFX S6b. ET-1, but not SFX S6c, als
o stimulated [H-3]arachidonic acid release by two-fold (EC50 = 3 +/- 0
.8 nM). Pretreatment of intact cells with neomycin or phorbol-12-myris
tate-13-acetate resulted in a 49% and 44% inhibition of ET-1-induced [
H-3]inositol phosphate accumulation but did not decrease ET-1-stimulat
ed [H-3]arachidonic acid release, suggesting that these responses are
separately regulated events in these cells.