Calcium mobilizing system coupled to endothelin A receptors (ETA) in Swiss 3T3, A10 and NRK cells

摘要

Endothelin (ET) is a potent vasoconstrictive peptide first isolated from the supernatant of a porcine aortic endothelial cell culture. Three forms of human ET (ET-1, -2, -3) have been reported, and two distinct ET receptor subtypes, ET, and ET,, have been characterized by molecular cloning. ETA receptors are highly selective for ET-1/ET-2, have lower affinity for ET-3, and are believed to be coupled to the phosphatidyl inositol-Ca2+ pathway. In this study, we investigated the signal transduction pathway induced by ET-I in three different cell lines, Swiss 3T3, A10 and NRK, which have ETA receptor. In A10 and NRK cells, ET-1 induced rapid generation of inositol 1,4,5-trisphosphates [Ins(1,4,5)P-3] and an increase in intracellular Ca2+ concentration ([Ca2+](i)). In Swiss 3T3 cells, gastrin-releasing peptide and generation and intracellular Ca2+ mobilization, and vasopressin induced both Ins(1,4,5)P-3 generation and intracellular Ca2+ mobilization, and generation of Ins(1,4,5)P-3 was more rapid than the increase in [Ca2+](i). In contrast, ET-I increased [Ca2+](i) as well as gastrin-releasing peptide and the increase was greater than that induced by vasopressin, but it caused little change in Ins(1,4,5)P-3 generation. Generation of other inositol phosphates including Ins(1,3,4)P-3 was induced by ET-1, but these phosphates increased after the elevation of [Ca2+](i) and had little effect on Ca2+ release from intracellular stores. Thus, this study suggests that the ETA receptors do not always couple to the same signal transduction system in different cells, and that Ins(1,4,5)P-3 does not play an important role in the ETA-induced rapid increase in [Ca2+](i) in Swiss 3T3 cells.