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 placent al stem villi vessels. All peptides examined, i.e. endothelin-1 (ET-1) , ET-3, sarafotoxin 6b (S6b) and S6c, were able to induce phosphoinosi tide hydrolysis in a dose-dependent manner; ET-1 was more potent than S6b and ET-3, with corresponding EC(50) 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- an d SGb-induced accumulation of inositol phosphate was almost totally (9 0%) inhibited by 100 mu mol/l BQ 123, while the S6c response was not a ffected by the ET(A) receptor antagonist, In contrast, the ET(B) recep tor antagonist IRL 1038 inhibited S6c-induced inositol phosphate accum ulation by more than 80%, whereas inhibition was only about 30% for ET -1 and S6b stimulations. This indicates that both ET(A) and ET(B) rece ptors were coupled to the phospholipase C transducing system in the mu scular layer of placental stem villi vessels, and there is evidence th at the phosphoinositide hydrolysis response is obtained predominantly via ET(A) receptor activation.