Synthesis and application of the photolabile guanosine 3′,5′-phosphoric-o-nitrobenzylester

Engels, Joachim W.; Reidys, R.

doi:10.1007/bf01921871

Cited by 25 publications

(19 citation statements)

References 6 publications

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“…The 2-nitrobenzyl esters by themselves are not hydrolyzed appreciably by cyclic AMPspecific phosphodiesterase from beef heart; they are weak inhibitors of phosphodiesterase at millimolar concentrations (37,58). At a concentration of 10 -6 M, the o-nitrobenzyl triester of cAMP had less than 10% of the activity of cAMP itself in a protein kinase assay, but full activity was obtained after photolysis (36). These observations indicate that 2-nitrobenzyl triesters bind slightly, or not at all, to intracellular cyclic nucleotide receptors.…”

Section: Cyclic Nucleotidesmentioning

confidence: 97%

See 1 more Smart Citation

Physiological and Pharmacological Manipulations with Light Flashes

Lester¹,

Nerbonne²

1982

Annu. Rev. Biophys. Bioeng.

115

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Section: Cyclic Nucleotidesmentioning

confidence: 97%

“…In the simplest o-nitrobenzyl derivative, R'= H, and the photolysis results in a nitroso aldehyde byproduct (36,37). This aldehyde apparently causes few problems at micromolar concentrations (37); but at higher concentrations it participates in further reactions that vitiate the compounds' usefulness.…”

Section: Cleavage Of Blocking Groupsmentioning

confidence: 99%

Physiological and Pharmacological Manipulations with Light Flashes

Lester¹,

Nerbonne²

1982

Annu. Rev. Biophys. Bioeng.

115

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“…The caged cAMPs and cGMPs commonly used up to now do not meet these requirements. The 2-nitrobenzyl, [2] 4,5-dimethoxy-2-nitrobenzyl (DMNB), [3] and 1-(2-nitrophenyl)ethyl (NPE) esters [4] photolyze relatively slowly and display rather low photoefficiencies. [5] Desoxybenzoinylcaged (desyl-caged) cAMP [6] is very sensitive to solvolysis in aqueous buffer solutions [7] and the (7-methoxycoumarin-4-yl)methyl esters of cAMP and cGMP [7,8] are poorly soluble.…”

mentioning

confidence: 99%

Highly Efficient and Ultrafast Phototriggers for cAMP and cGMP by Using Long-Wavelength UV/Vis-Activation

Hagen

Bendig

Frings

et al. 2001

Angew. Chem. Int. Ed.

160

141

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“…1) and its cGMP analog. These molecules are members of a group of phosphotriesters that enter cells (24)(25)(26). The o-nitrobenzyl esters can then be photolyzed to produce the cyclic nucleotides themselves, presumably within a few msec (27)(28)(29)(30).…”

mentioning

confidence: 99%

Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP.

Nargeot¹,

Nerbonne²,

Engels³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

119

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Voltage-clamped atrial trabeculae from bullfrog hearts were exposed to membrane-permeant photolyzable o-nitrobenzyl esters of cAMP and cGMP. UV flashes produced intracellular concentration jumps of cAMP or cGMP. With the cAMP derivative, flashes resulted in an increased slow inward current (Is;), producing a broadened action potential. The ISi reached a maximum 10-30 sec after the flash and decreased over the next 60-300 sec. The first increases were observable within 150 msec; this value is an upper limit imposed by the instrumentation. Responses to flashes lasted longer at higher drug concentrations and in the presence of the phosphodiesterase inhibitor papaverine; effects of flashes developed and decreased faster at higher temperature. Although the amplitude of the 'Si was increased, its waveform and voltage sensitivity were not affected. Intracellular concentration jumps of cAMP failed to affect the muscarinic K+ conductance. There were no observable effects of cGMP concentration jumps. The data confirm (i) that cAMP regulates the Ii and (ii) that the 5-to 10-sec delay between application of .8-agonists and the onset of positive inotropic effects, observed in previous studies, has been correctly ascribed to events prior to the interaction between cAMP and protein kdnase.Cyclic nucleotides are thought to play a pivotal role in the regulation of the strength and frequency of the heartbeat by autonomic neurotransmitters. Electrophysiological investigations show that such inotropic and chronotropic effects arise partly through changes in the slow inward current (Isi), which is carried mainly by calcium ions (1-5). The amplitude of the Isi is enhanced, and the plateau of the action potential is consequently lengthened, by many treatments that increase intracellular cAMP, such as /3-adrenergic stimulation (1, 3, 6), direct intracellular application of cAMP itself (5, 7-11), phosphodiesterase inhibition (12), exposure to membrane-permeant analogues of cAMP (13), and GTPase inhibition (14). On the other hand, this slow inward current is inhibited by muscarinic stimulation (4, 15, 16), which also inhibits adenylate cyclase (17,18 (22,23). Therefore, one expects that the positive inotropic effects would appear much more quickly in an experiment in which the intracellular cAMP concentration itself is jumped directly.We have therefore developed a method for producing concentration jumps of cyclic nucleotides within cells under physiological investigation. Our procedure exploits the properties of o-nitrobenzyl cAMP ( Fig. 1) and its cGMP analog. These molecules are members of a group of phosphotriesters that enter cells (24-26). The o-nitrobenzyl esters can then be photolyzed to produce the cyclic nucleotides themselves, presumably within a few msec (27-30). We find that the Is4 is indeed increased by photochemically generated concentration jumps of intracellular cAMP and that the latency of this action (< 150 msec) is no more than 3% of the latency for ,B-adrenergic stimulation.There are additional questions ab...

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Synthesis and application of the photolabile guanosine 3′,5′-phosphoric-o-nitrobenzylester

Cited by 25 publications

References 6 publications

Physiological and Pharmacological Manipulations with Light Flashes

Physiological and Pharmacological Manipulations with Light Flashes

Highly Efficient and Ultrafast Phototriggers for cAMP and cGMP by Using Long-Wavelength UV/Vis-Activation

Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP.

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