ONTOGENY OF ENDOTHELIN AND ITS RECEPTORS IN RAT-BRAIN

The ontogeny of endothelin (ET) system in rats was studied in preterm (18 days of gestation), term (21 days of gestation) and 1 week post term rats. Brains were dissected out and (1) processed for the estimation of endogenous ET-1 by RIA and (2) membranes were prepared for radioreceptor binding. Receptor characteristics, affinity (K(d)) and density (B(max)) were determined using [I-125] ET-1 and [I-125] SRT 6b (which is structurally similar to ET) and cold ET-1 or SRT 6b as displacer. ET levels were found to be 25.66 +/- 3.1 8 pg/g protein in preterm, 47.37 +/- 5.31 pg/g protein in term and 48.30 +/-1.90 pg/g protein in post term rats. ET levels were significantly lower in preterm as compared to term and post term rats. Preterm, term and post term rats showed single high affinity binding site for both [I-125] ET-1 and [I-125] SRT 6b. The K(d) values for [I-125] ET-1 and [I-125] SRT 6b binding were similar in preterm, term and post term rats. The B(max) values of both [I-125] ET-1 and [I-1 25] SRT 6b binding were found to be similar in preterm and term rats while they were significantly higher in post term rats. In adult (4 month old) rats the K(d) values were similar to neonatal rats while the B(max) values were significantly lower than the post term neonatal rats. It is concluded that ET and its receptors are developmentally regulated and there is a possibility that endogenous ET is involved in the regulation of ET receptor density.