Dopamine and the Kidney

Abstract

It would seem established beyond peradventure that dopamine is formed in the kidney from circulating L-dopa. The likely site would appear to be the renal tubular cells but the contribution of the renal dopaminergic nerves needs further evaluation. Moreover it is probably that dopamine formed within the kidney acts there on specific receptors. This results in vasodilatation of renal blood vessels, by action on vascular receptors, and natriuresis, by an effect on tubular sodium transport mechanisms. Dopamine may form an integral part of the renal natriuretic cascade by, in its turn, evoking both the kallikrein-bradykinin system and the production of renal prostaglandins. Specific activation of the renal dopaminergic system by the administration of suitable agonists or renal prodrugs may prove possible in the future. Abnormalities in the renal production of dopamine may be important in several hypertensive and oedematous disorders. Further work will be required to establish a possible role for dopamine in these conditions and to determine whether they will benefit from treatment with suitable dopamine agonists. Dopamine, once regarded as of little importance outside the central nervous system, has certainly come to occupy a central place in renal salt handling. The ratio of dopamine production in the kidney to that for renin may be of pivotal importance in the control of systemic arterial pressure.

Deamination of newly‐formed dopamine in rat renal tissues

“…The synthesis of dopamine, in renal tissues, has been suggested to occur either at neuronal and non-neuronal elements: in noradrenergic neurones, dopamine is the percursor for NA; in independent dopaminergic neurones, dopamine may serve as the transmitter substance (Bell, 1987) and there is evidence to suggest that in tubular epithelial cells, dopamine may act as a paracrine substance (Lee, 1982;Siragy et al, 1989). Thus, it might be suggested that decarboxylation of L-DOPA in renal tissues loaded with the amino acid can take place in each of these three cellular elements.…”

“…The results presented here show that a substantial amount of newly-formed dopamine is deaminated to DOPAC; this occurs largely in the renal cortex where saturation of deamination of dopamine could be observed, but also to some extent in the medulla and this difference may be related to the limited production of dopamine in the rat renal medulla. Alternatively, it could be hypothesized that in the rat renal medulla the specific activity of MAO may exceed that in the renal cortex, as has been found to occur in the kidney of the cat (Caramona & Soares-daSilva, 1990 In recent years, several lines of evidence have suggested that dopamine may exert considerable effects within the kidney and contribute actively in the maintenance of blood pressure at levels considered as acceptable (Lee, 1982;Yoshimura & Takahashi, 1988;Bertorello et al, 1988). The activation of -I type D1 dopamine receptors in the renal vasculature produced vasodilatation resulting in increased renal blood flow and glomerular filtration rate (Felder et al, 1988).…”

“…In kidney, a major source of dopamine derives from the decarboxylation of filtered 3,4-dihydroxyphenylalanine (DOPA) in tubular epithelial cells (Baines & Chan, 1980;Lee, 1982;Suzuki et al, 1984). This is a quantitatively important process as tubular epithelial cells have a high aromatic L-amino acid decarboxylase (AAAD) activity (Adam et al, 1986) and plasma levels of DOPA can attain concentrations up to 15 pmol ml 1 (Cuche, 1988).…”

Regional haemodynamic effects of dopamine and its prodrugs l‐dopa and gludopa in the rat and in the glycerol‐treated rat as a model for acute renal failure

“…Dopamine increases renal plasma flow and glomerular filtration rate through DA, receptor stimulation in efferent and afferent arteries (see for review e.g. Lee, 1982;Felder et al, 1989). Furthermore, DA, receptor stimulation results in normalization of the glomerular filtration rate (GFR) in a state of hyperfiltration caused by glycine (Wang Y.W.…”

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

“…synthesis in proximal tubular cells by the renal decarboxylation of L-dopa [12]. Similarly, it has been suggested that urinary 5-HT reflects intrarenal synthesis of 5-HT [2].…”