Atrial natriuretic factor alters phospholipid metabolism in mesangial cells.
The mechanism for the vasorelaxant effect of atrial natriuretic factor (ANF) remains to be clarified. Recent evidence suggests that this agent can antagonize the action of angiotensin II (ANG II) by affecting intracellular calcium metabolism. The biochemical basis for this phenomenon was investigated in cultured rat mesangial cells (MCs), a preparation which exhibits the contractile properties of smooth muscle cells and is responsive to ANG II and ANF. Preincubation of MCs with ANF significantly inhibited ANG II-induced release of inositol trisphosphate (IP3) resulting from hydrolysis of phosphatidylinositol 4, 5-bisphosphate. Similarly, ANG II-stimulated increases in cytosolic free Ca2+ [( Ca2+]i), 45Ca efflux, as well as 45Ca influx were diminished by ANF. In addition, these alterations in Ca2+ kinetics were associated with ANF-mediated antagonism of ANG II-induced phospholipid turnover and prostaglandin (PG) E2 release. Sodium nitroprusside (SNP), which augmented guanosine 3',5'-cyclic monophosphate (cGMP) accumulation to a degree comparable to ANF, likewise inhibited ANG II action on the phosphoinositide (PI) pathway, Ca2+ regulation, and PGE2 production. Collectively our results indicate that the effects of ANF on [Ca2+]i in MCs relate to cGMP-induced alterations of PI metabolism. In this fashion cGMP-elevating agents may influence a variety of calcium-dependent biochemical pathways including prostaglandin synthesis.
Department of Medicine, State University of New York, Stony Brook 11794.
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Barnett
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Ortiz
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Blaufox
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Singer
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Nord
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Ramsammy
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D000804:Angiotensin II; D009599:Nitroprusside; D016718:Arachidonic Acid; C016276:8-bromocyclic GMP; D000001:Calcimycin; D007294:Inositol; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine