Angiotensin II stimulation of phospholipase D in rat renal mesangial cells is mediated by the AT1 receptor subtype.
Angiotensin II stimulated a biphasic 1,2-diacylglycerol formation in [3H]arachidonic acid-labelled mesangial cells. In contrast, in cells labelled with [3H]myristic acid, a tracer that preferentially marks phosphatidylcholine, angiotensin II induced a delayed monophasic production of 1,2-diacylglycerol. This delayed peak of 1,2-diacylglycerol generation was associated with a concomitant increase in choline formation, suggesting that stimulation of mesangial cells with angiotensin II causes a phospholipase D-mediated phosphatidylcholine hydrolysis. This conclusion is supported by the observation that angiotensin II stimulated the accumulation of phosphatidylethanol, when ethanol was added to mesangial cells. The production of choline and phosphatidylethanol stimulated by angiotensin II was completely blocked by the angiotensin II AT1 receptor-selective antagonist DuP 753 with an IC50 value of 8 nM, but not by the angiotensin II AT2 receptor selective ligand CGP 42112A. Furthermore, angiotensin(1-7) and angiotensin(1-6) had only weak effects on choline generation. These data clearly indicate that angiotensin II AT1 receptors trigger phospholipase D-mediated phosphatidylcholine hydrolysis in rat mesangial cells.
Pfeilschifter
J
J
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Huwiler
A
A
Merriweather
C
C
Briner
V A
VA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000201:enzymology; D010739:Phospholipase D / Q000032:analysis*; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*
D004075:Diglycerides; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000431:Ethanol; D010739:Phospholipase D; D002794:Choline