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 microM). 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 microM), while the EC50 value for the other component remained unchanged. Sarafotoxin 6c (0.3 microM) 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 ETA receptor subtype, the other recognizing sarafotoxin 6c and endothelin-3, but not endothelin-1 and sarafotoxin 6b, being thus different from the ETB receptor subtype.
Harrison
V J
VJ
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Randriantsoa
A
A
Schoeffter
P
P
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology*; D017466:Receptors, Endothelin; D018000:Receptors, Peptide; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D017466:Receptors, Endothelin; D018000:Receptors, Peptide; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C058085:sarafotoxin receptor; C057354:sarafotoxins s6