scholarly journals Epac-mediated relaxation in murine basilar arteries depends on membrane permeability of cyclic nucleotide analogues and endothelial aging

2020 ◽  
Vol 39 (02) ◽  
pp. 157-168
Author(s):  
Johannes Welter ◽  
Gabriele Pfitzer ◽  
Olaf Grisk ◽  
Jürgen Hescheler, Lubomir T. Lubomirov
Keyword(s):  
Membrane Permeability ◽  
Cyclic Nucleotide ◽  
Nucleotide Analogues ◽  
Basilar Arteries

Effects of forskolin and cyclic nucleotides on isometric force in rat aorta

1986 ◽  
Vol 250 (3) ◽  
pp. C468-C473 ◽  
Author(s):  
E. G. McMahon ◽  
R. J. Paul
Keyword(s):  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Isometric Force ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Tension Development ◽  
Nucleotide Analogues ◽  
Cyclic Monophosphate ◽  
Contractile System ◽  
Rat Thoracic Aorta

The present study was undertaken to determine the extent to which cyclic nucleotide-induced relaxation in the intact rat aorta is mediated at the level of the contractile system. The relaxant effects of the cyclic nucleotide analogues [8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP)] and forskolin were examined in both the intact vessel and a Triton X-100-skinned preparation of rat thoracic aorta. Relaxation of a norepinephrine-induced contraction was essentially complete 30 min after the addition of 50 microM 8-BrcGMP [% relaxation = 87.2 +/- 4.4% (n = 4)], 100 microM DBcAMP [98.2 +/- 1.2% (n = 4)], and 1 microM forskolin [107.0 +/- 3.3% (n = 5)]. These same doses were ineffective in relaxing precontracted skinned rat aortic rings compared with the relaxation achieved in the intact vessel. The largest relaxation in the skinned aortas was achieved with the addition of 1 microM forskolin [17.4 +/- 1.5% (n = 4)]. The addition of catalytic subunit of cAMP-dependent protein kinase had no effect on isometric tension in the precontracted skinned aorta. Preincubation with the cyclic nucleotide analogues or forskolin in a low-Ca2+ solution (pCa less than 8) was also ineffective in inhibiting subsequent isometric tension development. Our results suggest that only a very small fraction of the relaxation with cyclic nucleotides and forskolin in the intact rat aorta is due to the action of these agents at the level of the contractile system.

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.

Opposite regulatory effects of cAMP and cGMP on sugar uptake in rat thymocytes

1987 ◽  
Vol 252 (5) ◽  
pp. E588-E594
Author(s):  
J. Segal
Keyword(s):  
Cyclic Nucleotide ◽  
Sugar Uptake ◽  
Dibutyryl Camp ◽  
Camp Concentration ◽  
Nucleotide Analogues ◽  
Cyclic Monophosphate ◽  
Regulatory Effects ◽  
Camp And Cgmp ◽  
Lines Of Evidence ◽  
Related Increase

The present study provides several lines of evidence which indicate that in the rat thymocyte adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5-cyclic monophosphate (cGMP) induce opposing regulatory effects on 2-deoxyglucose (2-DG) uptake; cAMP is stimulatory, whereas cGMP is inhibitory. First, the cyclic nucleotide analogues dibutyryl cAMP (dBcAMP) and dibutyryl cGMP (dBcGMP) produced a dose-related increase and decrease in thymocyte 2-DG uptake, respectively. Second, 3,5,3'-triiodo-L-thyronine (T3) and epinephrine, which increased cellular cAMP concentration but had no effect on cellular cGMP concentration, increased 2-DG uptake in the rat thymocyte. Third, dBcGMP inhibited the stimulatory effects of dBcAMP, T3, and epinephrine on thymocyte 2-DG uptake. Fourth, prostaglandin E1 and the inhibitors of the cyclic nucleotide phosphodiesterases, 3-isobutyl-1-methylxanthine, theophylline, and caffeine, all increased both cellular cAMP and cGMP concentration but had no effect on 2-DG uptake. Insulin did not change cellular cAMP and cGMP concentration, but produced a dose-related increase in 2-DG uptake by the rat thymocyte. From these results I have concluded that in the rat thymocyte cAMP and cGMP produce opposite effects on sugar uptake and that the effect of certain, but not all, agents on thymocyte sugar uptake results from their modulation of cellular cAMP and cGMP concentration.

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