Effects of isatin on atrial natriuretic peptide-mediated accumulation of cGMP and guanylyl cyclase activity of PC12 cells.
We have previously demonstrated that isatin (indole-2,3 dione), an endogenous compound widely distributed in mammalian tissues and body fluids, effectively inhibits atrial natriuretic peptide (ANP) receptor binding and ANP-stimulated guanylyl cyclase activity of rat membrane preparations. In the present study the effects of isatin on ANP-mediated accumulation of cGMP and guanylyl cyclase (GC) activity of PC12 cells were studied. Isatin (0.1 mM) effectively inhibited ANP-stimulated GC-activity of broken cells but was nearly inactive in attenuating ANP-dependent accumulation of cGMP in intact PC12 cells. The ATP-analogue adenylylimidodiphosphate (AMP-PNP) slightly potentiated the ANP effect on GC activity in broken cell preparations and significantly reduced GC sensitivity to isatin. Isatin caused a more pronounced reduction of ANP-dependent cGMP accumulation in cells grown in the presence of 10% embryonal calf serum (ECS) than in 0.5% ECS. The data obtained suggest that, in intact cells, the manifestation of the isatin effect on ANP-mediated signal transduction may depend on intracellular factor(s), possibly interacting at the kinase domain.
Medvede
A E
AE
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow. medvedev@ibmh.msk.su
Abakumova OYu
Podobed
O V
OV
Tsvetkova
T A
TA
Sandler
M
M
Glover
V
V
D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003470:Culture Media; D006152:Cyclic GMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D007510:Isatin / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
D003470:Culture Media; D000266:Adenylyl Imidodiphosphate; D007510:Isatin; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP