Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Angiotensin II stimulation of phospholipase D in rat renal mesangial cells is mediated by the AT1 receptor subtype. 154 25

Angiotensin stimulates a cellular mitogenic response via the AT1 receptor. We have examined the effect of angiotensin on the rate of phosphatidylcholine (PC) synthesis and have begun to dissect the pathway linking the AT1 receptor to the rate-limiting enzyme in PC synthesis, CTP: phosphocholine cytidylyltransferase (CCT), using CHO cells engineered to express the AT1a receptor. Since CCT can be directly activated by lipid mediators, we probed for their involvement in the PC synthesis response to angiotensin. Angiotensin stimulated CCT activity and PC synthesis two- to threefold after a 30-min delay. The kinetics of this stimulation most closely paralleled an increase in diacylglycerol (DAG) derived from myristic acid-enriched phospholipids. The production of arachidonic acid, phosphatidic acid, or reactive oxygen species either peaked much earlier or not at all. Moreover, manipulation of the intracellular supply of oxygen free radicals, arachidonic acid, HETEs, or phosphatidic acid (using inhibitors and/or exogenous addition) did not generate parallel effects on the rate of PC synthesis. Restricting the production of DAG by inhibition of PLCbeta with U73122 reduced both basal and angiotensin-stimulated PC synthesis. The U73122 inhibition of PC synthesis was accompanied by a similar inhibition of ERK1/2 phosphorylation. Addition of exogenous DAG stimulated basal and angiotensin-dependent PC synthesis, and partially reversed the effect of the PLC inhibitor on PC synthesis. These results do not provide support for lipid mediators as direct stimulators of CCT and PC synthesis downstream of angiotensin, but give rise to the idea that angiotensin effects might be mediated via ERK1/2.
 ...
PMID:Contribution of lipid mediators to the regulation of phosphatidylcholine synthesis by angiotensin. 1658 Aug 75