Endothelin-induced phosphoinositide hydrolysis in the muscular layer of stem villi vessels of human term placenta.
In the present study, we examined the relationship between endothelin receptors and phosphoinositide breakdown in muscle explants of placental stem villi vessels. All peptides examined, i.e. endothelin-1 (ET-1), ET-3, sarafotoxin 6b (S6b) and S6c, were able to induce phosphoinositide hydrolysis in a dose-dependent manner: ET-1 was more potent than S6b and ET-3, with corresponding EC50 values of 44 +/- 16 pmol/l, 18 +/- 13 nmol/l and 33 +/- 24 nmol/l, respectively. Sarafotoxin induced only moderate stimulation of inositol phosphate accumulation. Both ET-1- and S6b-induced accumulation of inositol phosphate was almost totally (90%) inhibited by 100 mumol/l BQ 123, while the S6c response was not affected by the ETA receptor antagonist. In contrast, the ETB receptor antagonist IRL 1038 inhibited S6c-induced inositol phosphate accumulation by more than 80%, whereas inhibition was only about 30% for ET-1 and S6b stimulations. This indicates that both ETA and ETB receptors were coupled to the phospholipase C transducing system in the muscular layer of placental stem villi vessels, and there is evidence that the phosphoinositide hydrolysis response is obtained predominantly via ETA receptor activation.
Mondon
F
F
INSERM U.361, Université René Descartes, Paris, France.
Doualla-Bell Kotto Maka
F
F
Sabry
S
S
Ferré
F
F
D000595:Amino Acid Sequence; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D017466:Receptors, Endothelin / Q000819:agonists / Q000032:analysis; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010716:Phosphatidylinositols; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C087220:BQ 610; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D010738:Type C Phospholipases; C072247:cyclo(Trp-Asp-Pro-Val-Leu)