ETA receptors mediate activation of phospholipases C and D in rat myometrium.
In estrogen-treated rat myometrium, endothelin-1 (ET-1) activated both the phospholipase C (PLC) which degrades PtdInsP2, resulting in an increased accumulation of inositol phosphates, and the phospholipase D pathway (PLD) as evidenced in the presence of butanol by an increased production of phosphatidylbutanol (PBut). Both ET-1 effects displayed similar concentration dependencies (EC50 50 nM) and were mediated by ET(A) receptors in that they were antagonized by BQ123 and were elicited by ET-3 with a rank order of potency ET-1 >> ET-3. Bombesin, another activator of the PLC/PtdInsP2 pathway, also increased PBut accumulation. Enhanced production of PBut could also be observed with the Ca2+ ionophore ionomycin and the phorbol ester PMA, an activator of protein kinase C, suggesting a potential contribution of the PLC/PtdInsP2 pathway in ET-1 induced PLD activity.
Dokhac
L
L
CNRS URA 1131, Université Paris-Sud, Orsay, France.
Le Stunff
H
H
Naze
S
S
Harbon
S
S
D000818:Animals; D016232:Endothelins / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D020404:Glycerophospholipids; D009215:Myometrium / Q000201:enzymology*; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*; D014590:Uterine Contraction / Q000187:drug effects
D016232:Endothelins; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C068564:phosphatidylbutanol; D010738:Type C Phospholipases; D010739:Phospholipase D