Juxtaglomerular Feedback JG Apparatus consists of three cell types: • Macula densa (TAL-DCT junction of same nephron) o Modified tubular epithelial cells • Juxtaglomerular cells (granular cells) o Produce renin in response to  β-1 adrenergic receptor stimulation  ↓Renal perfusion pressure as detected by the JG cells  ↑NaCl concentration at macula densa • Can be due to ↑GFR, or • Tubular reabsorption dysfunction o Located in the media of the AA entering the glomerulus  Extraglomerular mesangial cells If ↑NaCl concentration at MD: 1. ↑GFR or ↓PCT sodium and water reabsorption  ↑NaCl at MD 2. MD apical Na+/K+/2Cl- cotransporters (NKCC2) are exposed to tubular fluid and allow the increased Na to enter MD cells 3. The MD cells do not have enough Na+/K+ ATPases basolaterally to excrete this added Na  ↑cell osmolarity 4. Water enters cell via osmosis  cell swells  ATP escapes through basolateral, stretch-activated, non-selective Maxi-Anion channels. ATP is converted to adenosine (ADO) by ecto-5’nucleotidase 5. Adenosine constricts AA by binding with high affinity to A 1 receptors. Adenosine binds with lower affinity to A 2A and A2B receptors causing dilation of EA. A1 stimulation causes AA vasoconstriction by a complex intracellular mechanism which releases intracellular calcium in the JG cells, reducing renin secretion. This calcium moves into neighbouring AA cells via gap junctions, causing smooth muscle contraction and hence vasoconstriction This is called the TGF Calcium Wave. 6. AA vasoconstriction  ↑ pressure  ↓GFR If ↓NaCl concentration at MD: 1. ↓GFR or ↑PCT sodium and water reabsorption  ↓NaCl at MD because there was more time for the PCT to reabsorb NaCl) 2. NKCC2 has lower activity  complex signalling cascade  ↑PGE2 synthesis and release 3. PGE2 acts on receptors in the JG cells to cause renin release 4. Renin activates RAAS  ↑GFR