Effect of Serotonin Receptor Antagonist on Phosphate Excretion

. To determine whether endogenous intrarenal 5-hydroxytryptamine affects phosphate excretion, the serotonin receptor antagonist methiothepin (20 μg/kg, +6 μg/kg per h) was infused into the renal interstitium of rats fed a normal phosphate diet (0.7% phosphate [Pi]) in the presence of endogenous parathyroid hormone (PTH). Renal interstitial infusion of methiothepin significantly increased fractional phosphate excretion (FE Pi ) from 23 ± 4 to 30 ± 4% ( n = 8, P 0.05. In thyroparathyroidectomized rats fed a LPD, methiothepin infusion did not increase phosphate excretion (0.8 ± 0.4 to 1.3 ± 0.9%, n = 7, P > 0.05). However, the increase in FE Pi during PTH infusion was significantly greater in the presence of methiothepin (1.3 ± 0.9 to 20.0 ± 4.0%, Δ18.7 ± 3.5%) than in the vehicle-infused rats (0.5 ± 0.2 to 8.8 ± 1.1%, Δ8.3 ± 1.2%; n = 8, P < 0.05). In conclusion, these observations suggest that endogenous intrarenal serotonin enhances phosphate reabsorption in phosphate-replete rats, and attenuates the phosphaturic response to PTH in phosphate-deprived rats.