Efficacy of isatin analogues as antagonists of rat brain and heart atrial natriuretic peptide receptors coupled to particulate guanylyl cyclase

Isatin is an endogenous indole and an inhibitor of atrial natriuretic pepti de (ANP) receptors coupled with particulate guanylyl cyclase (GC). In this study, several isatin analogues were tested as inhibitors of ANP-stimulated GC in rat brain and heart membranes. None of these analogues affected acti vity in the absence of ANP, or stimulated ANP-induced activity. In both tis sues, some 5-substituted isatins (5-hydroxyisatin, 5-methylisatin, and 5-am inoisatin) exhibited more effective inhibitory activity than isatin itself, with IC50 values in the range 1.3-20 mu M. The efficacy of other analogues varied and was not consistent between the two tissues, raising the possibi lity of receptor heterogeneity and relative selectivity of inhibition. Some substituted isatins may have a role as pharmacological tools for investiga ting the physiological roles of natriuretic peptides and their receptors. B IOCHEM PHARMACOL 57;8:913-915, 1999. (C) 1999 Elsevier Science Inc.