Parathyroid hormone (PTH) increases serum calcium through multiple mechanisms. In the kidney, PTH acts on proximal and distal tubule cells. Which receptor-effector system primarily mediates PTH's effect on renal calcium reabsorption and phosphate excretion?

• A PTH1R (Gs-coupled) → cAMP → PKA activation, which inhibits NaPi-IIa phosphate cotransporter in proximal tubule and activates TRPV5 calcium channel in distal convoluted tubule ✓
• B PTH1R (Gq-coupled) → IP3 → Ca2+ release → CaM kinase activation → phosphatonin release
• C PTH2R on distal tubule → cGMP → PKG activation → TRPV6 channel opening for calcium reabsorption
• D PTH binding to megalin receptor on proximal tubule brush border activates Cl-/HCO3- exchange reducing phosphate reabsorption

Explanation

PTH acts primarily via PTH1R coupled to Gs protein, activating adenylyl cyclase and raising cAMP. In the proximal tubule, PKA phosphorylates and promotes endocytosis of NaPi-IIa (and NaPi-IIc) sodium-phosphate cotransporters from the brush border, reducing phosphate reabsorption and causing phosphaturia. In the distal convoluted tubule, PKA signaling enhances expression and activity of TRPV5 calcium channels on the apical membrane, increasing transcellular calcium reabsorption. PTH also stimulates 1-alpha-hydroxylase in the proximal tubule, increasing calcitriol synthesis, which further augments intestinal calcium absorption.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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