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

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Abstract
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.