Differential modulation of the renal proximal tubular DA-1 receptor by Gpp(NH)p and sodium in the spontaneously hypertensive rat.

1. In the normotensive rat (WKY) the guanine nucleotide, Gpp(NH)p, and sodium reduced the ability of the dopaminergic agonist fenoldopam to compete for the [3H]-SKF-38393 (dopamine-1 agonist) binding to the renal proximal tubular DA-1 receptors. 2. In the spontaneously hypertensive rat (SHR) Gpp(NH)p failed to reduce the affinity of fenoldopam for [3H]-SKF-38393 binding to renal tubular DA-1 receptors. 3. Sodium reduced the affinity of fenoldopam for [3H]-SKF-38393 binding in the SHR renal proximal tubular cells, but to a lesser extent than the WKY. 4. We conclude that the SHR has a defective DA-1 receptor or Gs/receptor coupling which interferes with the ability of Gpp(NH)p to act on the DA receptor/G protein complex.