title: The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness.
abstract: Cyclic nucleotide-gated (CNG) ion channels play a central role in vision and olfaction, generating the electrical responses to light in photoreceptors and to odorants in olfactory receptors. These channels have been detected in many other tissues where their functions are largely unclear. The use of gene knockouts and other methods have yielded some information, but there is a pressing need for potent and specific pharmacological agents directed at CNG channels. To date there has been very little systematic effort in this direction - most of what can be termed CNG channel pharmacology arose from testing reagents known to target protein kinases or other ion channels, or by accident when researchers were investigating other intracellular pathways that may regulate the activity of CNG channels. Predictably, these studies have not produced selective agents. However, taking advantage of emerging structural information and the increasing knowledge of the biophysical properties of these channels, some promising compounds and strategies have begun to emerge. In this review we discuss progress on two fronts, cyclic nucleotide analogs as both activators and competitive inhibitors, and inhibitors that target the pore or gating machinery of the channel. We also discuss the potential of these compounds for treating certain forms of retinal degeneration.
authors.affiliation: Neurological Sciences Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: R Lane
authors.initials: RL
authors.lastname: Brown
authors.forename: Timothy
authors.initials: T
authors.lastname: Strassmaier
authors.forename: James D
authors.initials: JD
authors.lastname: Brady
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Karpen
mesh_terms: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012162:Retinal Degeneration
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels