Decrease in endothelin-1 renal receptors during the 1st month of life in the rat

Endothelin-1 (Et1), like angiotensin II, is implicated in postnatal maturation and development, The present study was designed to identify Et1 receptors and subtype Et1 receptors present in rat kidney between 1 and 30 days of postnatal life. On day 1, high-affinity and high-density Et1 binding sites were identified in rat kidney. The dissociation constant and maximum binding for ET1 to membranes from whole kidney were 0.073+/-0.05 nM and 1,345.9+/-73 fmol/mg protein, respectively, On day 30, affinity and receptor density were markedly decreased. The dissociation constant and maximum binding were 0.147+/-0.021 nM (P<0.01) and 633.21+/-56.4 fmol/mg protein (P <0.001), respectively. Using BQ 123 (EtA-selective antagonist) and sarafotoxin S6c (EtB-selective agonist), the two Et1 receptor subtypes EtA and EtB were identified in 1- and 30-day-old rat kidney, BQ 123 selectively recognized EtA receptors with high affinity (2.9+/-0.44 on day 1 and 4.0+/-0.5 nM on-day 30) and sarafotoxin S6e bound with higher affinity EtB receptors (0.871+/-0.14 on day 1 and 0.717+/-0.12 nM on day 30). Between birth and day 30, the EtA binding capacity was decreased (304+/-27 vs. 752+/-202 fmol/mg protein, P <0.05), whereas EtB binding was not affected (514+/-87 vs. 656+/-171 fmol/mg protein, NS). The decrease in the total number of Et1 receptors during the Ist month of life may be due to the concomitant decrease in the number of EtA receptors. Increased Et1 receptor density in early postnatal life suggests an influence of Et1 on immature kidney circulation and/or kidney growth.