ISATIN IS A POTENT ENDOGENOUS ANTAGONIST OF GUANYLATE CYCLASE-COUPLED ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS

Isatin (indole-2,3-dione) is an endogenous compound with anxiogenic properties. In the brain, highest levels (0.1 mu g/g) have been found in the rat hippocampus. In the present study, we show that isatin has little effect on a wide range of neurotransmitter and hormonal receptors but that it acts as an inhibitor of atrial natriuretic peptide (ANP) binding, with an IC50 of 4x 10(-7)M. It also inhibits ANP-activated particulate guanylate cyclase from rat kidney, heart and brain membranes in dose-dependent fashion, varying also with ANP concentration. These findings suggest that isatin is a new endogenous regulator of mammalian ANP activity, with potential implications for the control of both anxiety and natriuresis.