DECREASE IN ENDOTHELIN-1 RENAL RECEPTORS DURING THE 1ST MONTH OF LIFEIN THE RAT

Endothelin-1 (Et1), like angiotensin II, is implicated in postnatal ma turation and development, The present study was designed to identify E t1 receptors and subtype Et1 receptors present in rat kidney between 1 and 30 days of postnatal life. On day 1, high-affinity and high-densi ty Et1 binding sites were identified in rat kidney. The dissociation c onstant and maximum binding for ET1 to membranes from whole kidney wer e 0.073+/-0.05 nM and 1,345.9+/-73 fmol/mg protein, respectively, On d ay 30, affinity and receptor density were markedly decreased. The diss ociation constant and maximum binding were 0.147+/-0.021 nM (P<0.01) a nd 633.21+/-56.4 fmol/mg protein (P <0.001), respectively. Using BQ 12 3 (EtA-selective antagonist) and sarafotoxin S6c (EtB-selective agonis t), the two Et1 receptor subtypes EtA and EtB were identified in 1- an d 30-day-old rat kidney, BQ 123 selectively recognized EtA receptors w ith 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+/-0.1 4 on day 1 and 0.717+/-0.12 nM on day 30). Between birth and day 30, t he 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 Et 1 receptors during the Ist month of life may be due to the concomitant decrease in the number of EtA receptors. Increased Et1 receptor densi ty in early postnatal life suggests an influence of Et1 on immature ki dney circulation and/or kidney growth.