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Cyclic nucleotide-gated (CNG) channels are expressed in many cell types in both the nervous system and nonexcitable tissues. In order to understand the roles of cGMP-gated channels, and to distinguish actions of cGMP mediated through CNG channels from those through cGMP-dependent protein kinase (G-kinase), several new cGMP analogs were tested for potency as CNG channel agonists. Using Xenopus oocytes expressing the rat rod cGMP-gated ion channel alpha-subunit, we showed that an analog containing a pCPT group at the 8-position, 8-pCPT-cGMP, was 80 times more potent than cGMP and 14 times more potent than 8-Br-cGMP. 8-pCPT-cGMP is the most potent CNG channel agonist so far described and also has the advantages of much better membrane permeability as well as much higher resistance to PDE-hydrolysis, as compared with 8-Br-cGMP. Modification of both 8-Br-cGMP and 8-pCPT-cGMP by introduction of a sulphur atom into the cyclic phosphate group gave smaller changes in agonist efficiency. Both Sp-8-Br-cGMPS and Sp-8-pCPT-cGMPS acted as agonists of CNG channels and are also G-kinase activators. In contrast, Rp-8-Br-cGMPS was a channel agonist, with an EC50 of 173.5 microM, but a G-kinase antagonist with a Ki of 4 microM. Finally, Rp-8-pCPT-cGMPS was a channel agonist and showed additional noncompetitive antagonist activity at higher concentrations. The results suggest that 8-pCPT-cGMPS is a highly potent photoreceptor CNG channel agonist with high membrane permeability and PDE-resistance and furthermore Rp-8-Br-cGMPS can be used to test whether the actions of cGMP are selectively mediated by CNG channels.
Ahmad,
Developmental and tissue-specific expression of the rod photoreceptor cGMP-gated ion channel gene.
1990, Pubmed
Ahmad,
Developmental and tissue-specific expression of the rod photoreceptor cGMP-gated ion channel gene.
1990,
Pubmed
Ahmad,
Retinal ganglion cells express a cGMP-gated cation conductance activatable by nitric oxide donors.
1994,
Pubmed
Ahmad,
Mouse cortical collecting duct cells show nonselective cation channel activity and express a gene related to the cGMP-gated rod photoreceptor channel.
1992,
Pubmed
Arancio,
Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons.
1996,
Pubmed
Arancio,
Activity-dependent long-term enhancement of transmitter release by presynaptic 3',5'-cyclic GMP in cultured hippocampal neurons.
1995,
Pubmed
Barnstable,
Isolation and characterization of the alpha-subunit of the rat rod photoreceptor cGMP-gated cation channel.
1995,
Pubmed
,
Xenbase
Baumann,
Primary structure and functional expression of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae.
1994,
Pubmed
,
Xenbase
Biel,
Molecular diversity of cyclic nucleotide-gated cation channels.
1995,
Pubmed
Bradley,
Functional expression of the heteromeric "olfactory" cyclic nucleotide-gated channel in the hippocampus: a potential effector of synaptic plasticity in brain neurons.
1997,
Pubmed
Brown,
Activation of retinal rod cGMP-gated channels: what makes for an effective 8-substituted derivative of cGMP?
1993,
Pubmed
Coburn,
A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans.
1996,
Pubmed
DiFrancesco,
Direct activation of cardiac pacemaker channels by intracellular cyclic AMP.
1991,
Pubmed
Ding,
Cloning and widespread distribution of the rat rod-type cyclic nucleotide-gated cation channel.
1997,
Pubmed
Distler,
Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells.
1994,
Pubmed
Dryer,
A cyclic GMP-activated channel in dissociated cells of the chick pineal gland.
1991,
Pubmed
Feng,
Expression of photoreceptor cyclic nucleotide-gated cation channel alpha subunit (CNGCalpha) in the liver and skeletal muscle.
1996,
Pubmed
Finn,
Cyclic nucleotide-gated ion channels: an extended family with diverse functions.
1996,
Pubmed
Goulding,
Molecular mechanism of cyclic-nucleotide-gated channel activation.
1994,
Pubmed
,
Xenbase
Goulding,
Role of H5 domain in determining pore diameter and ion permeation through cyclic nucleotide-gated channels.
1993,
Pubmed
,
Xenbase
Guy,
Similarities in amino acid sequences of Drosophila eag and cyclic nucleotide-gated channels.
1991,
Pubmed
Jan,
Tracing the roots of ion channels.
1992,
Pubmed
Jan,
A superfamily of ion channels.
1990,
Pubmed
Kaupp,
Family of cyclic nucleotide gated ion channels.
1995,
Pubmed
Kawada,
cGMP-kinase mediates cGMP- and cAMP-induced Ca2+ desensitization of skinned rat artery.
1997,
Pubmed
Kingston,
Rat hippocampal neurons express genes for both rod retinal and olfactory cyclic nucleotide-gated channels: novel targets for cAMP/cGMP function.
1996,
Pubmed
Koch,
Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism.
1985,
Pubmed
Komatsu,
Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans.
1996,
Pubmed
Kramer,
Antagonists of cyclic nucleotide-gated channels and molecular mapping of their site of action.
1996,
Pubmed
Kumar,
Molecular model of the cyclic GMP-binding domain of the cyclic GMP-gated ion channel.
1992,
Pubmed
Leinders-Zufall,
Block of cyclic nucleotide-gated channels in salamander olfactory receptor neurons by the guanylyl cyclase inhibitor LY83583.
1995,
Pubmed
Leinders-Zufall,
A calcium-permeable cGMP-activated cation conductance in hippocampal neurons.
1995,
Pubmed
Liu,
Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.
1996,
Pubmed
McKay,
Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA.
1981,
Pubmed
Misaka,
Taste buds have a cyclic nucleotide-activated channel, CNGgust.
1997,
Pubmed
Nawy,
Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells.
1990,
Pubmed
Oda,
Alternatively spliced forms of the cGMP-gated channel in human keratinocytes.
1997,
Pubmed
Santoro,
Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels.
1997,
Pubmed
Scott,
Predicted ligand interactions of 3'5'-cyclic nucleotide-gated channel binding sites: comparison of retina and olfactory binding site models.
1996,
Pubmed
Shabb,
Cyclic nucleotide-binding domains in proteins having diverse functions.
1992,
Pubmed
Shiells,
Glutamate receptors of rod bipolar cells are linked to a cyclic GMP cascade via a G-protein.
1990,
Pubmed
Thompson,
Cyclic GMP-gated channels in a sympathetic neuron cell line.
1997,
Pubmed
Varnum,
Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels.
1995,
Pubmed
Wei,
Identification of competitive antagonists of the rod photoreceptor cGMP-gated cation channel: beta-phenyl-1,N2-etheno-substituted cGMP analogues as probes of the cGMP-binding site.
1996,
Pubmed
,
Xenbase
Wei,
Molecular and pharmacological analysis of cyclic nucleotide-gated channel function in the central nervous system.
1998,
Pubmed
Wei,
Direct blockade of both cloned rat rod photoreceptor cyclic nucleotide-gated non-selective cation (CNG) channel alpha-subunit and native CNG channels from Xenopus rod outer segments by H-8, a non-specific cyclic nucleotide-dependent protein kinase inhibitor.
1997,
Pubmed
,
Xenbase
Weyand,
Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm.
1994,
Pubmed
,
Xenbase
Wilson,
2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans.
1994,
Pubmed
Yau,
Cyclic nucleotide-gated channels: an expanding new family of ion channels.
1994,
Pubmed
Zagotta,
Structure and function of cyclic nucleotide-gated channels.
1996,
Pubmed
Zimmerman,
Interaction of hydrolysis-resistant analogs of cyclic GMP with the phosphodiesterase and light-sensitive channel of retinal rod outer segments.
1985,
Pubmed
Zufall,
Cyclic nucleotide gated channels as regulators of CNS development and plasticity.
1997,
Pubmed
