Proximal tubule dopamine histofluorescence in renal slices incubated with L -dopa

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.

Section: Discussionmentioning

confidence: 99%

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

MacDonald

Jeffrey

Freestone

et al. 1988

“…The basis of its relative renal specificity lies in the sequential conversion to dopamine by the actions of y-glutamyl transfer- (Hagege & Richet, 1985) and there is much evidence to suggest that urine dopamine is principally derived, under normal conditions, from the uptake and decarboxylation of circulating Ldopa in proximal tubular cells (Lee, 1986). Worth et al (1985) have previously demonstrated that gludopa increases renal blood flow and glomerular filtration rate with a small reduction in filtration fraction.…”

Section: Discussionmentioning

confidence: 99%

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

Jeffrey

MacDonald

Brown

et al. 1988

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.

“…In these previous studies therefore a reduction in the inhibitory effect of All on dopamine excretion might have offset the effect of reduced natriuresis. All is known to act on the proximal tubule to stimulate sodium resorption (Navar et al, 1987) and it is known that this is the site of renal dopamine formation (Hagege & Richet, 1985). Dopamine decreases sodium resorption in the pars recta of the proximal tubule (Bello- Reuss et al, 1982) by acting on specific receptors (Felder et al, 1984) so an inhibitory effect of AII on dopamine excretion at this site is feasible.…”

Section: Discussionmentioning

confidence: 99%

Frusemide, ACE inhibition, renal dopamine and prostaglandins: acute interactions in normal man.

MacDonald¹,

Craig²,

Watson³

1989

1 The acute effects of intravenous frusemide (30 mg) on prostaglandin dependent renal haemodynamics, urinary prostaglandin excretion, urinary dopamine excretion and electrolyte excretion were studied in six salt replete healthy volunteers with and without pretreatment with the angiotensin converting enzyme (ACE) inhibitor, ramipril (5 mg) and compared with the effects of ramipril alone in order to clarify the role of the reninangiotensin system in these responses.2 Frusemide increased natriuresis (UNaV), kaliuresis (UKV), inulin clearance and plasma renin activity (PRA) and ramipril pretreatment significantly enhanced these effects suggesting that the acute generation of angiotensin II (All) may attenuate these actions of intravenous frusemide.3 Frusemide increased para-aminohippurate (PAH) clearance, osmolar clearance and urine flow but did not change filtration fraction or urinary kallikrein excretion. Pretreatment with ramipril did not affect these responses. 4 Frusemide increased the excretion of urinary PGE2 and 6-keto-PGFia. Ramipril pretreatment did not suppress this rise in prostaglandin excretion. Since the frusemide induced prostaglandin dependent renal haemodynamic changes were also not suppressed with ACE inhibition, this suggests that in salt-replete volunteers All does not significantly modulate renal prostaglandin production after frusemide. 5 Urinary free dopamine excretion increased with frusemide alone. With ramipril pretreatment this rise showed a tendency to increase. All may therefore inhibit the rise in urinary dopamine excretion after frusemide. However this requires further study.