Ontogeny of DA1 receptor-adenylate cyclase coupling in proximal convoluted tubules

The natriuretic effect of dopamine (DA) is less in younger than in older animals. The natriuretic (DA) is less in younger than in older animals. The natriuretic effect of DA is due in part to occupation of renal tubular DA1 receptors, which are most abundant in the proximal convoluted tubule (PCT). However, it has not been determined whether ontogenic differences in DA1-receptor density, affinity, or coupling to intracellular second messengers are involved in the reduced natriuretic effect of DA in the young animal. We therefore studied the DA1 receptor by radioligand binding with the DA1 antagonist 125I-SCH 23982 and the effect of DA1 agonists and guanine nucleotides on adenylate cyclase (AC) activity in microdissected PCT during development in Wistar-Kyoto rats (WKY). The dissociation constant (Kd) and maximum receptor density (Bmax) were similar in all groups (Kd, in nM: 11.9 +/- 0.7 at 3 wk, 10.6 +/- 0.4 at 8 wk, and 12.2 +/- 1.2 at 20 wk; Bmax, in fmol/mm PCT: 0.24 +/- 0.02 at 3 wk, 0.23 +/- 0.01 at 8 wk, and 0.24 +/- 0.01 at 20 wk). Basal AC activities were similar, and forskolin (10(-5) M), which directly stimulates AC, increased AC activity to a similar extent in all age groups. However, the DA1 agonists, fenoldopam (10(-5) M) and SND-919-CL2 (10(-6) M), increased AC activity in PCT to a greater extent in 20-wk-old (55 +/- 7%) than in 3-wk-old rats (27 +/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)