Formation of Serotonin by Rat Kidneys in Vivo

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Abstract
Renal formation of serotonin by decarboxylation of its amino acid precursor L-5-hydroxytryptophan (L-5-HTP) has been demonstrated with renal tissue homogenates and isolated perfused rat kidneys. Our objective in the present study was to determine whether the conversion of L-5-HTP to serotonin was associated with functional changes by kidneys in vivo. Renal clearance studies were conducted in anesthetized, volume-expanded male Sprague-Dawley rats receiving either saline (n = 9) or L-5-HTP (15 and 75 .mu.g/min, n = 9). No change in mean arterial pressure was measured during infusions of L-5-HTP at either dose, whereas glomerular filtration rate (GFR), as measured by the clearance of inulin, and effective renal plasma flow (CPAH) decreased by 34 .+-. 5% (mean .+-. SE, P < 0.001) and 26 .+-. 7% (P < 0.07), respectively. Urine flow and sodium excretion decreased by 41 .+-. 9% (P < 0.01). Serotonin and 5-HTP were determined in urine and plasma using HPLC. High levels of 5-HTP were present in plasma, but not urine. Urinary serotonin increased in the rats receiving L-5-HTP without concomitant increases in plasma serotonin. More than 20% of the infused L-5-HTP was recovered in the urine as serotonin. The decarboxylase inhibitor carbidopa (20 .mu.g/min) markedly reduced urinary serotonin excretion in the rats which received L-5-HTP and reversed the changes in GFR, CPAH, urine flow, and sodium excretion. Infusions of the amino acid precorsor of L-5-HTP, L-tryptophan (n = 7), did not alter kidney function or increase plasma or urinary 5-HTP or serotonin levels. These results are consistent with the intrarenal formation of serotonin by renal decarboxylase with attendant alterations in renal hemodynamics and salt and water excretion.