Effect of serotonin receptor antagonist on phosphate excretion

To determine whether endogenous intrarenal 5-hydroxytryptamine affects phosphate excretion, the serotonin receptor antagonist methiothepin (20 microgram/kg, +6 microgram/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). To determine whether serotonin modulates the phosphaturic response to PTH during conditions of dietary phosphate excess or deprivation, rats were fed either a high (1.8% Pi, HPD) or low (0.07% Pi, LPD) phosphate diet, and methiothepin (100 microgram/kg, +30 microgram/kg per h) or saline vehicle was infused intravenously before and during PTH infusion (33 U/kg, +1 U/kg per min). Methiothepin infusion significantly increased FE(Pi) in thyroparathyroidectomized rats fed a HPD from 25 +/- 4 to 32 +/- 4% (n = 9, P < 0.05), and the subsequent administration of PTH further increased the FE(Pi) to 64 +/- 3% (P < 0.05). The increase in FE(Pi) during PTH infusion was similar in the absence (Delta27 +/- 5%, n = 7) and presence (Delta33 +/- 6%) of methiothepin, 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%, Delta18.7 +/- 3.5%) than in the vehicle-infused rats (0.5 +/- 0.2 to 8.8 +/- 1.1%, Delta8.3 +/- 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.