Thomas Linto, Bettoni Carla, Knöpfel Thomas, Hernando Nati, Biber Jürg, Wagner Carsten A
Institute of Physiology, University of Zurich, Zurich, Switzerland; and National Centre for Competence in Research, Zurich, Switzerland.
Institute of Physiology, University of Zurich, Zurich, Switzerland; and National Centre for Competence in Research, Zurich, Switzerland
J Am Soc Nephrol. 2017 Mar;28(3):903-914. doi: 10.1681/ASN.2016010082. Epub 2016 Oct 6.
Phosphate (Pi) homeostasis is regulated by renal, intestinal, and endocrine mechanisms through which Pi intake stimulates parathyroid hormone (PTH) and fibroblast growth factor-23 secretion, increasing phosphaturia. Mechanisms underlying the early adaptive phase and the role of the intestine, however, remain ill defined. We investigated mineral, endocrine, and renal responses during the first 4 hours after intravenous and intragastric Pi loading in rats. Intravenous Pi loading (0.5 mmol) caused a transient rise in plasma Pi levels and creatinine clearance and an increase in phosphaturia within 10 minutes. Plasma calcium levels fell and PTH levels increased within 10 minutes and remained low or high, respectively. Fibroblast growth factor-23, 1,25-(OH)-vitamin D, and insulin concentrations did not respond, but plasma dopamine levels increased by 4 hours. In comparison, gastric Pi loading elicited similar but delayed phosphaturia and endocrine responses but did not affect plasma mineral levels. Either intravenous or gastric loading led to decreased expression and activity of renal Pi transporters after 4 hours. In parathyroidectomized rats, however, only intravenous Pi loading caused phosphaturia, which was blunted and transient compared with that in intact rats. Intravenous but not gastric Pi loading in parathyroidectomized rats also led to higher creatinine clearance and lower plasma calcium levels but did not reduce the expression or activity of Pi transporters. This evidence suggests that an intravenous or intestinal Pi bolus causes rapid phosphaturia through mechanisms requiring PTH and downregulation of renal Pi transporters but does not support a role of the intestine in stimulating renal clearance of Pi.
磷酸盐（Pi）稳态通过肾脏、肠道和内分泌机制进行调节，Pi摄入通过这些机制刺激甲状旁腺激素（PTH）和成纤维细胞生长因子-23的分泌，从而增加尿磷排泄。然而，早期适应阶段的潜在机制以及肠道的作用仍不明确。我们研究了大鼠静脉注射和胃内给予Pi负荷后最初4小时内的矿物质、内分泌和肾脏反应。静脉注射Pi负荷（0.5 mmol）导致血浆Pi水平和肌酐清除率短暂升高，并在10分钟内尿磷排泄增加。血浆钙水平在10分钟内下降，PTH水平在10分钟内升高，并分别保持在低水平或高水平。成纤维细胞生长因子-23、1,25-（OH）-维生素D和胰岛素浓度无反应，但血浆多巴胺水平在4小时时升高。相比之下，胃内给予Pi负荷引起类似但延迟的尿磷排泄和内分泌反应，但不影响血浆矿物质水平。4小时后，静脉注射或胃内给予Pi负荷均导致肾脏Pi转运体的表达和活性降低。然而，在甲状旁腺切除的大鼠中，只有静脉注射Pi负荷导致尿磷排泄，与完整大鼠相比，这种排泄减弱且短暂。甲状旁腺切除的大鼠静脉注射而非胃内给予Pi负荷也导致肌酐清除率升高和血浆钙水平降低，但并未降低Pi转运体的表达或活性。这一证据表明，静脉注射或肠道给予Pi推注通过需要PTH和下调肾脏Pi转运体的机制导致快速尿磷排泄，但不支持肠道在刺激肾脏清除Pi方面的作用。
