1. Vishnevskii Institute of Surgery, Russian Academy of Medical Sciences 2. Institute of Reproductive and Developmental Biology, Imperial College London 3. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
Abstract: Isatin is an endogenous indole, which is increased in mammalian brain and peripheral tissues under conditions of stress. Physiological concentrations of isatin inhibit natriuretic peptide (NPR) receptor binding and NPR-dependent signalling. The inhibition of NPR signalling by isatin is attenuated by a nonhydrolyzable ATP analogue. In this study we have demonstrated that short term incubation of rat brain synaptosomes with a physiological concentration of isatin caused a rapid 3-fold accumulation of ATP. The additional increase of ATP in the presence of tyrphostin, an inhibitor of tyrosine kinase, which uses ATP for phosphorylation of some proteins, suggests the dependence of this phenomenon on the activity of ATP-consuming systems. ATP inhibited binding of [3H]isatin to both particulate and soluble fractions of the rat brain. These results suggest that isatin induces accumulation of ATP, which in turn may displace isatin from both membrane-bound and soluble binding sites. Since natriuretic peptides are known to decrease stress hormone release this regulatory loop may be involved in the maintenance of natriuretic peptide signalling under conditions of stress and thus contribute to the control of stress responses.
Reference: Globa A.G., Glover V., Medvedev A.E., Isatin causes a rapid accumulation of ATP in synaptosomes: implication for stress and regulation of natriuretic peptide receptors, Biomeditsinskaya khimiya, 2008, vol:
1. Medvedev A., Igosheva N., Crumeyrolle-Arias M., Glover V. (2005) Stress, 8, 175-183. CrossRef
2. Medvedev A.E., Buneeva O.A., Glover V. (2007) Biological Targets and Therapeutics, 1(2), 151-162.
3. Mawatari K., Segawa M., Masatsuka R., Hanawa Y., Iinuma F., Watanabe M. (2001) Analyst, 126, 33-36. CrossRef