Natriuretic peptide interaction with [3H]isatin binding sites in rat brain.
Isatin is an endogenous indole, which has a distinct and discontinuous distribution in the brain and exhibits a wide range of physiological and pharmacological effects. In the present study, we have demonstrated that atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) inhibited [3H]isatin binding to rat brain sections and isolated membrane fractions. Isatin itself antagonised not only natriuretic peptide receptor type A (NPR-A) (ANP-stimulation of guanylyl cyclase) but also NPR-C (ANP and CNP mediated inhibition of adenylyl cyclase) signalling. These results suggest that some [3H]isatin binding in the brain may be to NPR-A and NPR-C. Competitive interactions between isatin and natriuretic peptides and their receptors give a possible explanation of the known anxiogenic effect of low doses of isatin, interacting at NPR-A, and the sedative effects of higher doses, antagonising respectively the anxiolytic effect of ANP and the anxiogenic effect of CNP.
Medvedev
Alexei
A
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, 10 Pogodinskaya Str., 19992 Moscow, Russia.
Crumeyrolle-Arias
Michele
M
Cardona
Anna
A
Sandler
Merton
M
Glover
Vivette
V
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007510:Isatin / Q000378:metabolism*; D045265:Natriuretic Peptides / Q000378:metabolism*; D051381:Rats; D014316:Tritium / Q000378:metabolism
D045265:Natriuretic Peptides; D014316:Tritium; D007510:Isatin