title: Kinetics of vasoconstrictor action of endothelins.
abstract: Endothelin peptides (Et) induce slowly developing and long-lasting contractions of rat aortic strips with a rank order of potency (Et-1 = Et-2 greater than sarafotoxin S6b greater than Et-3) consistent with the involvement of an EtA-like receptor subtype. A similar profile of action is observed for Et-induced intracellular [Ca2+]i mobilization in cultured aortic myocytes. Modeling the association of Et-1 to its receptor shows that, at concentrations which produce large increases in tension, Et-1 associates rapidly to its receptors and that a slow rate of association is not responsible for the slow rate of tension development. Action of endothelins on [Ca2+]i was studied using isolated cultured aortic myocytes and compared with that of angiotensin II and vasopressin. Results show that three vasoconstrictors produce similar and rapid changes in [Ca2+]i. The rate-limiting step for the contractile action of Et is a postreceptor event probably distal to early changes in [Ca2+]i. Biological responses to Et are usually characterized by a relative insensitivity to the peptide as compared with Kd values determined in binding experiments. Data presented show that insensitivity of the early [Ca2+]i responses to Et could be accounted for by the fact that the responses develop under nonequilibrium conditions. Tension amplitude seems also to be determined by non-equilibrium binding conditions. It correlates with the fraction of the Et-1 binding sites occupied 20 s after addition of the peptide and not to the fractional site occupancy at the time of maximum tension development.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: R
authors.initials: R
authors.lastname: Marsault
authors.forename: P
authors.initials: P
authors.lastname: Vigne
authors.forename: J P
authors.initials: JP
authors.lastname: Breittmayer
authors.forename: C
authors.initials: C
authors.lastname: Frelin
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001127:Arginine Vasopressin / Q000502:physiology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000502:physiology*; D005260:Female; D005453:Fluorescence; D007700:Kinetics; D051381:Rats; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface / Q000378:metabolism; D017466:Receptors, Endothelin; D015398:Signal Transduction; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D000804:Angiotensin II; D001127:Arginine Vasopressin; D002118:Calcium