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

Abstract

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 633.2 +/- 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 S6c 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 1st 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.

Muscular ETBReceptors Develop Postnatally and Are Differentially Distributed in Specific Segments of the Rat Vasculature

“…In addition to the pulmonary circulation, information on the developmental aspects of ET-receptor expression or function in the rat is very limited. In rat kidney, Abadie and coworkers reported a decrease of ET A receptor-binding capacity during the first month of life, while binding to the ET B receptor was not affected (Abadie et al 1996). However, no data on the cellular distribution of the ET-receptor subtypes were provided.…”

Low NaCl intake elevates renal medullary endothelin‐1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na+ excretion to ETA receptor blockade in rats

“…2003). Renal receptor binding of the ET A receptor antagonist BQ123 is reduced to less than half between postnatal days 1–30 in rats (Abadie et al. 1996) suggesting that ET A receptors also play a role in renal development and structural adaptations to environmental changes.…”

The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney

“…Increased ET receptor density in early postnatal life suggests an influence of ET-1 on immature kidney circulation and/or kidney growth [ 15 ]. Yoo et al showed that the inhibition of endogenous ETs by the administration of an antagonist of ET A receptors to neonate rats impairs renal growth, with decreased cellular proliferation and increased apoptosis in the kidneys [ 16 ].…”