The Royal Infirmary, Edinburgh EH3 9YW 1 y-L-glutamyl-L-dopa (gludopa) was given by intravenous infusion to six healthy saltreplete men on two occasions, with and without pretreatment with (+)-sulpiride. 2 Gludopa increased sodium excretion, glomerular filtration rate and effective renal plasma flow whilst decreasing plasma renin activity. 3 (+)-sulpiride had no significant effect on baseline natriuresis, renal haemodynamics or plasma renin activity, but significantly attenuated the rise in sodium excretion, glomerular filtration rate and effective renal plasma flow produced by gludopa. 4 (+)-sulpiride abolished the acute fall in plasma renin activity seen with gludopa. 5 (+)-sulpiride raised serum prolactin concentration but did not affect the rise in urine dopamine excretion rate caused by gludopa. 6 Gludopa exerts its renal effects by stimulating specific dopamine receptors which are principally of the DA1 subtype.

1. The effect of oral lithium on the renal response to gamma‐L‐glutamyl‐ L‐dopa (gludopa, 25 micrograms kg‐1 min‐1) was investigated in seven normal males. 2. Gludopa at this dose produced an 800‐fold increase in urine dopamine excretion. It was natriuretic and suppressed plasma renin activity without altering blood pressure and pulse. 3. Lithium alone increased sodium excretion and stimulated plasma renin activity. However, it abolished the natriuresis produced by gludopa. 4. Gludopa did not significantly affect lithium clearance. 5. This study suggests that lithium interacts with dopamine at the proximal tubule and that the lithium clearance method is not suitable for investigating dopaminergic mechanisms in the kidney.

1 The renal response to y-L-glutamyl-L-dopa (gludopa, 25 ,ug kg-1 min-') was investigated in seven normal male volunteers. The effects of oral carbidopa (100 mg) and indomethacin (100 mg) on the response to gludopa were studied in the same group. 2 Gludopa at this dose level produced a 900-fold increase in urine dopamine excretion and caused a natriuresis and suppression of plasma renin activity with only minor effects on pulse rate and blood pressure. 3 Carbidopa inhibited the increase in dopamine excretion by 97% and abolished the renal actions of gludopa. 4 The increase in urine dopamine produced by gludopa was not altered by indomethacin and the urine sodium output was similar to that caused by gludopa alone. 5 Gludopa is an effective renal dopamine prodrug whose activity can be blocked by the dopa decarboxylase inhibitor carbidopa. The results with indomethacin suggest that dopamine and the prostaglandins form separate natriuretic systems in the kidney.

1. The urine dopamine response to intravenous frusemide (30 mg) was investigated in 15 salt replete male volunteers. The effects of oral indomethacin (100 mg) and oral carbidopa (100 mg) given before intravenous frusemide were studied in the same group of subjects. 2. Frusemide produced a significant increase in urine dopamine output within 15 min. 3. Indomethacin attenuated the natriuretic and renin responses to frusemide, but did not alter urine dopamine output. 4. Carbidopa lowered urine dopamine to undetectable levels, but did not significantly affect the natriuretic and renin responses to frusemide. 5. We conclude that urine dopamine excretion after frusemide is not directly related to increased sodium excretion or renin response and it is not mediated by the prostaglandins. In addition, dopamine does not contribute to the renal actions of frusemide under normal conditions.

The Royal Infirmary, Edinburgh EH3 9YW 1 y-L-glutamyl-L-dopa (gludopa) and placebo were given by intravenous infusion to 12 healthy salt replete men for 10 h in a single-blind randomised fashion. 2 Gludopa caused a cumulative natriuresis of 46.5 mmol compared with placebo with a biphasic pattern and this was associated with a small reduction in body weight. 3 A small fall in arterial blood pressure and rise in pulse rate was seen with gludopa. 4 Plasma renin activity, atrial natriuretic peptide and urine kallikrein excretion were unchanged by gludopa but a small fall in urine aldosterone excretion, urine flow rate and free water clearance occurred. 5 The renal effects of gludopa are modest and last for only a few hours after the start of infusion.