Interaction of isatin with type-A natriuretic peptide receptor: possible mechanism.

The effect of isatin on rat brain particulate guanylate cyclase (GC) was investigated. The enzyme was stimulated by atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and urodilatin, but not by C-type natriuretic peptide (CNP). Their effects were not additive, pointing to action via the GC-A receptor. Isatin, in dose-dependent manner, abolished this stimulation. The non-hydrolysable ATP analogue, adenylylimidodiphosphate, potentiated the effects of submaximal doses of ANP, BNP and urodilatin on this particulate GC-A, and attenuated or abolished sensitivity to isatin. These results suggest that isatin antagonises the generation of second messenger by GC-A; this sensitivity might be regulated at an ATP binding site, possibly a protein kinase-like domain.