Extended data 1 fig .pdf

Extended Data Figure 1 | Schematic showing potential mechanism involved in GABA-, glycine- and glutamate-mediated changes in vessel diameter. Diagrams show a pericyte, with claw like processes, situated on a blood vessel in close proximity to Loop of Henle (LOH). GABA, glutamate (Glut) and glycine (Glyc) are supplied from the blood, tubular cells, endothelial cells and urine. a, Activation of GABAAR on pericytes causes an increase in [Ca2+]I through L-type VOCC and release from [Ca2+]I stores. Likewise, activation of GABAARs likely stimulates the production of IP3, which binds to IP3R and induces Ca2+ release from the endoplasmic reticulum stores. Elevation of [Ca2+]i leads to calcium and calmodulin (CaM)-dependent activation of myosin light chain kinase (MLCK) in pericytes. This leads to contraction by phosphorylation of MLC and promotes interaction of α-smooth muscle actin (SMA). b, Glutamate and Glycine simultaneously bind to and activate inotropic glutamate receptors, NMDA receptors (NMDAR), on endothelial and/or tubule epithelial cells. Activation of NMDARs causes an increase in [Ca2+]I leading to the synthesis of nitric oxide (NO). NO diffuses to pericytes, supressing the synthesis of vasoconstrictor 20-HETE and triggering PGE2, which stimulates pericyte mediated vasodilation of capillaries via EP4 receptors (EP4R).