The slow development of contractile responses to endothelins is determined by postreceptor events rather than the kinetics of receptor binding.
Endothelin peptides (Et) induce slowly developing and long-lasting contractions of rat aortic strips with a rank order of potency (Et-1 = Et-2 > sarafotoxin S6b > 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 flow cytometry; intracellular calcium; kinetic model; vasopressin Submitted on October 25, 1990 Accepted on June 14, 1991
Marsault et al. (Sun,) studied this question.
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