Decreased tubular uptake of L-3,4-dihydroxyphenylalanine in streptozotocin-induced diabetic rats

Abstract

Background/aims: This study determined alterations in renal dopamine production in streptozotocin-treated rats and explored the mechanisms underlying this alteration.

Methods: Streptozotocin (65 mg/kg) or vehicle was administered to 3-month-old male Wistar rats. Treated animals had hyperglycemia, glycosuria and increased diuresis, natriuresis and excretion of L-dopa. Urinary dopamine and dihydroxyphenylacetic acid were similar to those in control animals. The production of dopamine by renal cortex slices from treated rats was significantly less than that from control animals. The addition of glucose (8.4-18.4 mM) to the incubation medium decreased about 40% the uptake of L-dopa by isolated proximal tubular cells. Scatchard analysis of the saturation curves obtained in this condition showed a decrease in the V(max) without changes in the K(m).

Results: Our results confirm previous studies suggesting a renal dopaminergic deficiency in insulin-dependent diabetes and provide evidence strongly suggesting that a decrease in the number of tubular L-dopa transport sites is the underlying defect of this deficiency.

Conclusion: These results highlight the role of the uptake of dopa as an important modulator of renal dopamine synthesis.