HS-142-1, a novel antagonist for natriuretic peptides, has no effect on the third member of membrane bound guanylate cyclases (GC-C) in T84 cells.

HS-142-1, a novel non-peptide antagonist for natriuretic peptides, exerts antagonistic actions almost equally on two similar guanylate cyclase-linked natriuretic peptide receptors (GC-A and GC-B), but has little or no effect on the binding of natriuretic peptides to a membrane protein, the so-called "clearance receptor", which binds all natriuretic peptides. The third mammalian form of membrane bound guanylate cyclases (GC-C) was identified not as a natriuretic peptide receptor, but as a receptor for heat-stable enterotoxins (STa). In this study, we examined effects of HS-142-1 on GC-C (STaR) in T84 cells and showed that HS-142-1 exerts neither agonistic nor antagonistic activity for GC-C, indicating that HS-142-1 is not a common antagonist for a family of membrane bound guanylate cyclase receptors, but a specific antagonist for the guanylate cyclase-linked natriuretic peptide receptors.