Dopamine receptors in the proximal tubule of the rabbit

Abstract

Our laboratory has characterized dopamine receptors in glomeruli and tubular homogenates. Since the heterogeneity of kidney homogenates limits the interpretation of these studies, the [3H]haloperidol binding site and adenylate cyclase sensitivity to dopamine were studied in the isolated proximal convoluted tubule and pars recta of the rabbit kidney. [3H]Haloperidol binding sites were saturable, stereoselective, and of high affinity. The apparent dissociation constant was 31.5 X 10(-9) M (+/- 8.5) and the maximum receptor density was 0.31 X 10(-15) M (+/- 0.08) per millimeter. In pars recta specific binding was 53% of total [3H]-haloperidol binding. Dopamine stimulated adenylate cyclase activity in a dose-related manner, which was inhibited by cis-flupenthixol but not by trans-flupenthixol or (-)-propranolol. Moreover, the stimulatory effect of the dopamine 1 (D1) agonist SKF 82526 on adenylate cyclase activity was blocked by the D1 antagonist SCH 23390. Dopamine receptors in the proximal convoluted tubule appear to be of the D1 subtype since they are linked to stimulation of adenylate cyclase. This is further substantiated by the stereoselectivity for (+)-sulpiride (a D1 antagonist), which had a greater affinity for the [3H]haloperidol binding site than (-)-sulpiride (a D2 antagonist).

(+)‐sulpiride antagonises the renal effects of gamma‐L‐glutamyl‐L‐dopa in man.

“…This may be due to high intrarenal concentrations of dopamine overcoming the DA1-receptor antagonism in a competitive manner with time. This may occur preferentially at the proximal tubular receptors (Felder et al, 1984) close to the site at which dopamine is thought to be generated (Hagege & Richet, 1985) and secreted (Baines & Chan, 1980). Serum sulpiride concentrations were falling throughout the gludopa infusion and may have contributed to an increasing effect of gludopa.…”

The effect of lithium on the renal response to the dopamine prodrug gludopa in normal man.

“…Early in vivo studies suggested that dopamine may also exert specific effects on tubular salt handling (McGiff & Bums, 1967) and this question has more recently been addressed by in vitro tubular preparation techniques. Dopamine receptors have been identified on proximal tubular cells (Felder et al, 1984) and Bello-Reus et al (1982) . Dopamine stimulates cAMP synthesis in the rat kidney particulate preparation (Nakajima et al, 1977) and an increase in urine cAMP has been measured after dopamine infusion in man (Vlachoyannis et al, 1976).…”

Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat.

“…PCT was microdissected from male 18-20-wk-old SHR (mean arterial pressure 166.6±2.7 mmHg, n = 9) and WKY (mean arterial pressure 11 1.3±1.5 mmHg, n = 9) (Harlan-Sprague Dawley, Inc., Indianapolis, IN) according to the procedure previously described from this laboratory (17,18). In a separate group of experiments 3-wk-old WKY and SHR were used.…”

“…We have previously reported the presence of DA-1 receptors coupled to stimulation of adenylate cyclase in the PCT of the rabbit ( 17) and rat kidney ( 18). These receptors are also present in proximal straight tubule (17)(18)(19)(20) and cortical collecting duct (16,19).…”