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.
Keywords: cGMP, Polymer-linked ligand dimers (PLDs), Dichlorobenzamil (DCB), CNGA1 Channels, HCN channels
Current Pharmaceutical Design
Title: The Pharmacology of Cyclic Nucleotide-Gated Channels: Emerging from the Darkness
Volume: 12 Issue: 28
Author(s): R. Lane Brown, Timothy Strassmaier, James D. Brady and Jeffrey W. Karpen
Affiliation:
Keywords: cGMP, Polymer-linked ligand dimers (PLDs), Dichlorobenzamil (DCB), CNGA1 Channels, HCN channels
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.
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Cite this article as:
Lane Brown R., Strassmaier Timothy, Brady D. James and Karpen W. Jeffrey, The Pharmacology of Cyclic Nucleotide-Gated Channels: Emerging from the Darkness, Current Pharmaceutical Design 2006; 12 (28) . https://dx.doi.org/10.2174/138161206778522100
DOI https://dx.doi.org/10.2174/138161206778522100 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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