23] Applications of caged compounds of hydrolysis-resistant analogs of cAMP and cGMP

Abstract

Publisher Summary Cyclic nucleotides—that is, cAMP and cGMP—control a variety of important cellular processes. The study of cAMP- and cGMP-signaling pathways has been greatly facilitated by the design of chemical derivatives, dubbed “caged”compounds. Caged cAMP and caged cGMP have also been used to study the activation kinetics of the cGMP-gated channel from rod photoreceptor cells, the signaling pathways in olfactory sensory neurons (OSNs), 15'16 the enhancement of CI – currents in ventricular cells, and the motile response of fish melanophores. This chapter discusses the properties of these compounds and their usefulness for electrophysiological studies of cyclic nucleotide-gated (CNG) channels in situ using heterologously expressed α subunits of CNG channels from bovine OSNs and cone photoreceptor cells. For many physiological studies, it would be desirable to use caged compounds that liberate cAMP or cGMP derivatives that are hydrolysis resistant or have higher biological efficiency. Derivatives that meet both these criteria are 8-Br-cAMP and 8-Br-cGMP. They are poorly hydrolyzable by phosphodiesterases, and 8-Br-cGMP activates cGK and CNG channels more effectively than cGMP.