scholarly journals Cyclic Nucleotide (cNMP) Analogues: Past, Present and Future

2021 ◽  
Vol 22 (23) ◽  
pp. 12879
Author(s):  
Erik Maronde
Keyword(s):  
Cyclic Nucleotide ◽  
Second Messengers ◽  
Nucleotide Analogues ◽  
Drug Candidates ◽  
Physiological Signal ◽  
Cellular Events ◽  
Current State ◽  
Dependent Protein ◽  
Target Molecules ◽  
Basic And Applied Research

Cyclic nucleotides are important second messengers involved in cellular events, and analogues of this type of molecules are promising drug candidates. Some cyclic nucleotide analogues have become standard tools for the investigation of biochemical and physiological signal transduction pathways, such as the Rp-diastereomers of adenosine and guanosine 3′,5′-cyclic monophosphorothioate, which are competitive inhibitors of cAMP- and cGMP-dependent protein kinases. Next generation analogues exhibit a higher membrane permeability, increased resistance against degradation, and improved target specificity, or are caged or photoactivatable for fast and/or targeted cellular imaging. Novel specific nucleotide analogues activating or inhibiting cyclic nucleotide-dependent ion channels, EPAC/GEF proteins, and bacterial target molecules have been developed, opening new avenues for basic and applied research. This review provides an overview of the current state of the field, what can be expected in the future and some practical considerations for the use of cyclic nucleotide analogues in biological systems.

scholarly journals Cyclic nucleotide regulation of teleost rod photoreceptor inner segment length.

1993 ◽  
Vol 102 (1) ◽  
pp. 75-98 ◽  
Author(s):  
B A Liepe ◽  
B Burnside
Keyword(s):  
Cyclic Nucleotide ◽  
Intracellular Signaling ◽  
Kinase Inhibitor ◽  
Segment Length ◽  
Rod Photoreceptor ◽  
Lepomis Cyanellus ◽  
Nucleotide Analogues ◽  
Intracellular Signals ◽  
Dependent Protein ◽  
Nucleotide Regulation

Retinal rod photoreceptors of teleost fish elongate in the light and shorten in the dark. Rod cell elongation and shortening are both mediated by actin-dependent mechanisms that occur in the inner segment myoid and ellipsoid. The intracellular signaling pathways by which light and dark regulate the actin cytoskeleton in the inner segment are unknown. To investigate the intracellular signals that regulate teleost rod motility, we have been using mechanically isolated rod inner/outer segments (RIS-ROS) obtained from the retinas of green sunfish, Lepomis cyanellus. In culture, RIS-ROS retain the ability to elongate in response to light; myoids elongate 15-20 microns in length during 45 min of light culture. A pharmacological approach was taken to investigate the role of cyclic nucleotides, cyclic nucleotide-dependent kinases, and protein phosphatases in the regulation of RIS-ROS motility. Millimolar concentrations of cAMP and cGMP analogues were both found to inhibit light-induced myoid elongation and two cyclic nucleotide analogues, SpCAMPS and 8BrcGMP, promoted myoid shortening after RIS-ROS had elongated in response to light. The cyclic nucleotide-dependent kinase inhibitor, H8, mimicked light by promoting myoid elongation in the dark. The effects of H8 were dose dependent, with maximal elongation occurring at concentrations of approximately 100 microM. Similar to the effects of cyclic nucleotide analogues, the phosphatase inhibitor, okadaic acid (0.1-10 microM), inhibited light-induced elongation and promoted shortening. The results presented here suggest that RIS-ROS motility is regulated by protein phosphorylation: phosphorylation in the dark by cyclic nucleotide-dependent protein kinases promotes rod shortening, while dephosphorylation in the light promotes rod elongation.

scholarly journals Cyclic nucleotide-dependent protein kinases in airway smooth muscle.

1982 ◽  
Vol 257 (19) ◽  
pp. 11609-11616 ◽  
Author(s):  
T J Torphy ◽  
W B Freese ◽  
G A Rinard ◽  
L L Brunton ◽  
S E Mayer
Keyword(s):  
Smooth Muscle ◽  
Protein Kinases ◽  
Airway Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Dependent Protein

scholarly journals Cyclic Nucleotide-dependent Protein Kinases

1969 ◽  
Vol 244 (23) ◽  
pp. 6395-6402 ◽  
Author(s):  
Eishichi Miyamoto ◽  
J.F. Kuo ◽  
Paul Greengard
Keyword(s):  
Protein Kinases ◽  
Cyclic Nucleotide ◽  
Dependent Protein

scholarly journals Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Major Function ◽  
Surface Receptors ◽  
Dependent Protein

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

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