Effects of isatin on atrial natriuretic peptide-mediated accumulation of cGMP and guanylyl cyclase activity of PC12 cells.

Abstract:

: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.

journal_name

Life Sci

journal_title

Life sciences

authors

Medvede AE,Abakumova OYu,Podobed OV,Tsvetkova TA,Sandler M,Glover V

doi

10.1016/s0024-3205(01)01270-x

subject

Has Abstract

pub_date

2001-08-31 00:00:00

pages

1783-90

issue

15

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(01)01270-X

journal_volume

69

pub_type

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