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.