HETEROGENEITY OF ENDOTHELIN-SARAFOTOXIN RECEPTORS MEDIATING CONTRACTION OF PIG CORONARY-ARTERY

The contractile effects of endothelin-1, endothelin-3, sarafotoxin 6b and sarafotoxin 6c were studied in endothelium-denuded rings of pig coronary artery. Endothelin-1, sarafotoxin 6b and sarafotoxin 6c produced monophasic concentration-response curves (mean EC50 values 6.7, 14.8 and 1.6 nM), whereas the concentration-response curve to endothelin-3 was biphasic (mean EC50 values 9.6 nM and 0.32-mu-M). The maximal effect of sarafotoxin 6c was about one third of that reached by the other peptides. The higher sensitivity component of the curve to endothelin-3 was abolished in the presence of sarafotoxin 6c (0.3-mu-M), while the EC50 value for the other component remained unchanged. Sarafotoxin 6c (0.3-mu-M) failed to alter the EC50 values of endothelin-1 and sarafotoxin 6b. These data strongly suggest the presence of at least two endothelin-sarafotoxin receptors mediating contraction of pig coronary artery, one with the profile of the endothelin ET(A) receptor subtype, the other recognizing sarafotoxin 6c and endothelin-3, but not endothelin-1 and sarafotoxin 6b, being thus different from the ET(B) receptor subtype.