title: Calcium-dependent activation of phospholipase C by mechanical distension in renin-expressing As4.1 cells.
abstract: One of the major physiological regulators for the production and release of renin from the kidney is blood pressure. The juxtaglomerular (JG) cells, located primarily at the afferent arterioles leading to the glomerulus, are thought to be the baroreceptor of the kidney and adjust their ability to secrete renin in an inverse relationship to changes in pressure (mechanical force). The characteristics of JG cells that allow them to sense and respond to changes in mechanical force at the cellular level are not clear. By use of a renin-expressing clonal cell line (As4.1) as a model for JG cells, it was the purpose of this paper to identify cellular pathways that are activated by mechanical distension. Fura 2-labeled As4.1 cells were mechanically probed to observe changes of intracellular calcium concentration ([Ca(2+)](i)). Mechanical distension of As4.1 cells resulted in an influx of Ca(2+) to the cytosol, mediated by stretch-activated ion channels and dependent on the presence of extracellular Ca(2+). Furthermore, cyclic mechanical distension elevated total inositol phosphates (IP) in As4.1 cells. This response was also dependent on the presence of extracellular Ca(2+), and the addition of U-73122, a phospholipase C (PLC) antagonist, significantly attenuated the increase of IP. Taken together, these findings demonstrate the calcium-dependent activation of PLC and the subsequent increase of IP and [Ca(2+)](i) to be a potentially important pathway for the modality of pressure sensing by renin-expressing cells in response to mechanical stimulation.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, 14214, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ryan
authors.forename: K W
authors.initials: KW
authors.lastname: Gross
authors.forename: G
authors.initials: G
authors.lastname: Hajduczok
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D005682:Gadolinium / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012083:Renin / Q000096:biosynthesis*; D012433:Ryanodine / Q000494:pharmacology; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004963:Estrenes; D005456:Fluorescent Dyes; D007473:Ion Channels; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D005682:Gadolinium; D010738:Type C Phospholipases; D012083:Renin; D002118:Calcium; D016257:Fura-2