Phospholipase D contributes to transmural pressure control of prorenin processing in juxtaglomerular cell.
This study was designed to delineate the involvement of phospholipase C (PLC) and phospholipase D (PLD) in transmural pressure control of renin synthesis and secretion. Primary cultures of rat juxtaglomerular (JG) cells were applied to a transmural pressure-loading apparatus for 12 hours, and the renin secretion rate (RSR), active renin content (ARC), and total (active + inactive) renin content (TRC) were determined. Under control conditions (n=5), transmural pressure decreased RSR (78.1 +/- 3.0 and 64.6 +/- 4.4% for 0 or 40 mm Hg, respectively; P<0.05) and ARC (42.8 +/- 3.3 and 26.0 +/- 3.9 ng of angiotensin I per hour per million cells for 0 or 40 mm Hg, respectively; P<0.05) but did not have a significant effect on TRC (99.5 +/- 6.7 and 89.2 +/- 4.6 ng of angiotensin I per hour per million cells for 0 or 40 mm Hg, respectively). Treatment with PLC inhibitors, 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate (200 micromol/L) and U73122 (10 micromol/L) did not alter RSR but prevented the RSR decrease with transmural pressure, whereas neither 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate nor U73122 altered ARC, TRC, or the decrease in ARC with transmural pressure. Experiments were also performed using JG cells (n=5) treated with a PLD inhibitor, 4-(2-aminoethyl)-benzensulfonyl fluoride (AEBSF, 100 micromol/L). Treatment with AEBSF did not influence basal levels of RSR, ARC, and TRC or the RSR decrease with transmural pressure. However, AEBSF did inhibit the decrease in ARC with transmural pressure. These results indicate that transmural pressure inhibits renin secretion via PLC-dependent pathways and prevents conversion of inactive renin to active renin via PLD-dependent mechanisms in JG cells.
Hirota
Nobuhisa
N
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Ichihara
Atsuhiro
A
Koura
Yukako
Y
Hayashi
Matsuhiko
M
Saruta
Takao
T
D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D010739:Phospholipase D / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D000991:Antithrombins; D004792:Enzyme Precursors; D004963:Estrenes; D011760:Pyrrolidinones; D013450:Sulfones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D010738:Type C Phospholipases; D010739:Phospholipase D; D012083:Renin