The protective effect of atrial natriuretic peptide (ANP) on cells damaged by oxygen radicals is mediated through elevated CGMP-levels, reduction of calcium-inflow and probably G-proteins.
ANP increases cellular cGMP content in cultured hepatocytes and decreases Ca2(+)-inflow in a concentration- and time-dependent manner which explains a beneficial effect on hypoxia cell injury (25). Both observations are mimicked by SNP and 8-Br-cGMP and blocked by Ly 83583 indicating a cGMP-mediated mechanism. The protective effect was also inhibited by Pertussis Toxin (PT) without lowering the elevated cGMP-level. But PT in combination with ANP leads to a higher Ca2(+)-inflow. Stimulated Na(+)-inflows are also be lowered by ANP. Here, neither SNP can mimick nor PT can inhibit this effect. Our results now indicate that the beneficial effect by ANP at the cellular level is mediated through cGMP which decreases calcium-inflow. ANP seems to control Ca2(+)-channels direct via a PT-sensitive G-protein and indirect by a cGMP-mediated mechanism and Na(+)-channels cGMP-independent through a PT-insensitive G-protein, thus preventing cells on hypoxia and oxygen radicals.
Pella
R
R
Department of Biological Chemistry, Faculty of Biology, Konstanz, Germany.
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D005609:Free Radicals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D000860:Hypoxia; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000634:Aminoquinolines; D005609:Free Radicals; D010566:Virulence Factors, Bordetella; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D006997:Hypochlorous Acid; D009320:Atrial Natriuretic Factor; C041715:6-anilino-5,8-quinolinedione; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium