2006B11 List the hormones that regulate tubular reabsorption and describe their action and site of action.

Hormone

Effect

Renin

·   Enzymatic cleavage angiotensinogen -> angiotensin 1 (precursor to AT2)

·   No direct effect

Angiotensin 2

·   Cellular: AGTR – G_q G protein-coupled receptor (GPCR) -> ↑IP₃/Ca²⁺, ↑DAG

·   Tubule: ↑Na⁺/HCO₃^-/H₂O reabsorption at proximal tubule

·   Vascular: constrict efferent > afferent arterioles -> ↓peritubular hydrostatic pressure -> ↑reabsorption

·   CNS: ↑ADH release (see below)

Aldosterone

·   Cellular: mineralocorticoid receptor – transcription factor -> ↑↓gene expression

·   Principal cell: ↑Na⁺K⁺ATPase synthesis and activity -> ↑ENaC and ROMK activity-> ↑Na⁺/↓K⁺ reabsorption

·   Type 1 intercalated cell: ↑H⁺ATPase activity -> ↓H+ reabsorption

·   Indirect effect: ↑ECF osmolality -> ↑ADH -> ↑H₂O reabsorption

·   Cortisol causes same effects but to a lesser extent

ADH

·   Cellular: V2R – G_s GPCR -> ↑cAMP

·   Collecting ducts: insert aquaporins into apical membrane -> ↑H₂O reabsorption

·   Medullary collecting ducts: insert ureaporins into apical membrane -> urea recycling -> ↑interstitial osmolality -> facilitate H₂O absorption

·   Thick ascending loop of Henle: ↑Na⁺ reabsorption

ANP

·   Vascular: dilate afferent and efferent arterioles -> ↑GFR, ↑vasa recta flow, ↑washout of medullary interstitium -> ↓reabsorption

·   Distal tubule: inhibit NCC -> ↓Na⁺Cl^- reabsorption

·   Collecting duct: inhibit ENaC -> ↓Na⁺ reabsorption

Adrenaline

·   Cellular: β₁ G_s GPCR -> ↑Ca²⁺; α₁ G_q GPCR -> ↑cAMP

·   Vascular (β₁): juxtaglomerular cell -> ↑renin-angiotensin-aldosterone activity (see above)

·   Proximal tubule (α₁): ↑Na⁺/HCO₃^- absorption

PTH

·   Cellular: PTHR: G_s GPCR -> ↑cAMP

·   Proximal tubule: ↓PO₄^3- reabsorption

·   Distal tubule: ↑Ca²⁺ reabsorption

Vitamin D₃

·   Cellular: VDR - nuclear transcription factor -> ↑↓gene transcription

·   Proximal tubule: ↑PO₄^3- reabsorption

·   Distal tubule: ↑Ca²⁺ reabsorption

Calcitonin

·   Cellular: CTR – GPCR multiple types

·   Proximal tubule: ↓PO₄^3- reabsorption

·   Distal tubule: ↓Ca²⁺ reabsorption