Atriopeptins and nitroprusside provoke opposite changes in cGMP and cAMP levels in human macrophages.
Atrial natriuretic factor (ANF, 10(-7) M) and, even more potently, sodium nitroprusside (SNP, 10(-5)-10(-3) M) stimulated cGMP formation in human peritoneal macrophages. This suggests that the two forms of guanylate cyclase, the particulate form stimulated by ANF and the soluble form activated by SNP, coexist in this cell type. A fall in cAMP levels in parallel with the rise of cGMP levels provoked by ANF and SNP was noticed that was amplified by an increase in the concentration of the phosphodiesterase inhibitor, IBMX. Our finding that ANF, contrary to its action in other tissues, was unable to exert direct inhibitory effects on the adenylate cyclase activity in isolated macrophage membranes, together with the observation that SNP was able to mimic the effect of ANF on cAMP levels indicates that the cAMP-lowering effect of ANF is most likely mediated through the cGMP signal.
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
A P
AP
Houdijk
M J
MJ
Adolfs
I L
IL
Bonta
H R
HR
De Jonge
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D005292:Ferricyanides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects
D005292:Ferricyanides; D011506:Proteins; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine