Decrease in endothelin-1 renal receptors during the 1st month of life in the rat
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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.
Key wordsRat Neonate Kidney Endothelin Receptors
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- 4.Nambi P, Pullen M, Wu HL, Nambi A, Ohlstein EH, Edwards RM (1992) Identification of endothelin receptor subtypes in human renal cortex and medulla using subtype-selective ligands. Endocrinology 131: 1080–1086Google Scholar
- 7.Roubert P, Gillard-Roubert V, Pourmarin L, Cornet S, Guilmard C, Plas P, Pirotzky E, Chabrier PE, Braquet P (1995) Endothelin receptor subtypes, EtA and EtB, are upregulated in an experimental model of acute renal failure. Mol Pharmacol 45: 182–188Google Scholar
- 13.De Nucci G, Thomas R, D'Orléans-Juste P, Autunes E, Walder C, Warner TD, Vane JR (1988) Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA 85: 9797–9800PubMedGoogle Scholar
- 15.Kogan BA, Bogaert G, Mevorach RA, Gluckman GR, Wong J (1994) Endothelin-1 causes renal vasodilation in the fetal lamb (abstract). J Am Soc Nephrol 5: 589Google Scholar
- 20.Fant ME, Nanu L, Word RA (1992) A potential role for endothelin-1 in human placental growth: interactions with the insulin-like growth factor family of peptides. J Clin Endocrinol Metab 7: 1158–1163Google Scholar