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 microgram/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.
D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D007510:Isatin / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*
D008996:Monoamine Oxidase Inhibitors; D007510:Isatin; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor