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Updated: Aug 19, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Hormonal induction of low affinity receptor guanylyl cyclase
J R Jewett1, K J Koller, D V Goeddel
1Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
Abstract:
We describe a unique transient binding phenomenon for atrial natriuretic peptide (ANP) binding to the natriuretic peptide receptor-A (NPR-A) guanylyl cyclase stably expressed in 293 cells. The time course of ANP binding to intact cells peaked at 15 min followed by a subsequent decrease. Reduced binding was a consequence of an ANP induced low affinity state of NPR-A, and required the receptors' kinase homology domain. In a particulate fraction, ANP-stimulated cGMP production was dependent on ATP as a cofactor, and ATP promoted a lower affinity state. Our findings suggest that the kinase homology domain of NPR-A mediates the regulatory action of ATP, not only for signal transduction, but in the modulation of NPR-A hormone affinity.
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