8- Bromo-cAMP

Recent work in our laboratory (Kompella, Mathias, and Lee, unpublished observation) has revealed that activation of the cAMP-regulated Cl channels in the conjunctiva also enhances the transcytosis of horseradish peroxidase. 8-Bromo-cAMP (a membrane-permeable analog of cAMP) and terbutaline (a p2-adrenergic agonist known to increase intracellular levels of cAMP in other epithelial tissues [238]), at 0.5 mM, were found to enhance the transport of 100 pg/ mL HRP from the mucosal side to the serosal side of the pigmented rabbit conjunctiva by a factor of 4 (Fig. 11). 

Figure 11 Influence of intracellular elevation of cAMP on the fluid-phase transport of HRP in the rabbit conjunctiva. Terb = terbutaline 8BrcAMP = 8-bromo cAMP. Error bars denote mean SEM. for n = 4. (Kompella, Mathias, and Lee, unpublished data.)...

Other protein kinases may indirectly influence the activation of NF-kappap. For example, in contrast to the pro-inflammatory effects typically observed with activation of kinases, the elevation ofcAMP activates PKA and blocks transcription of iNOS mRNA [51,178, 229, 230]. Astrocytes contain a variety of NT receptors that are coupled to Gs-adenylate cyclase [231] and, either activation of P-adrenergic/dopamine receptors or employing agents that increase cAMP, such as forskolin (adenylate cyclase activator), PDE inhibitors [i.e. pentoxifylline], dibutyrl cAMP, or 8-bromo cAMP can attenuate lipopolysaccharide (LPS)/cytokine activated iNOS mRNA in microglia, astrocytes and a number of other cell types [51,176,177,178, 232-237]. In contrast, agents that suppress the intracellular concentration of cAM P such as H-89 and Rp-cAM P are pro-... 

Several studies have revealed that the D2 receptors modulate the state of phosphorylation of DARPP-32. In mouse striatal slices, the D2 agonist quinpirole decreased the basal phosphorylation of DARPP-32 on Thr-34, and antagonized the phosphorylation produced by the application of D1 agonist, forskolin or 8-bromo-cAMP (Nishi et al., 1997). This D2 effect was calcium-dependent and was blocked by cyclosporine A, an inhibitor of calcineurin, suggesting that it involved an increase in intracellular Ca2+ and a dephosphorylation of DARPP-32 by calcineurin. This study showed that an activation of... 

Bld-HrTH administration to B. discoidalis in vivo or to isolated fat body fails to stimulate either fat body cAMP levels or adenylate cyclase activity and supports the previous findings (25). Nevertheless, for B. discoidalis, fat body phosphorylase activity is elevated and trehalose levels increase both in vivo and in vitro, and calcium is essential in vitro in addition to Bld-HrTH. No stimulation of trehalose synthesis is noted with agents that elevate adenylate cyclase, such as forskolin, or by inhibitors of phosphodiesterase such as theophylline or isobutylmethylxanthine (IBMX). Additions of cAMP, dibutyryl cAMP or 8-bromo-cAMP are not stimulatory to trehalose synthesis either in vivo or in vitro. This same result was observed for P. americana in that neither cAMP nor dbcAMP stimulated trehalose production by fat body in vitro, and xanthine inhibitors of phosphodiesterase that should cause accumulation of intracellular cAMP were inhibitory, except for isobutylmethylxanthine (IBMX) which was stimulatory for unknown reasons (26). We have not observed a stimulatory effect by IBMX with B. discoidalis fat body in vitro. 

Schaeffer R Jr, Bitrick M Jr. Effects of human a-thrombin and 8-bromo-cAMP on large and microvessel endothelial monolayer equivalent pore radii. Microvasc Res 1995 49 364. 

The synthesis of two novel caged compounds, 4,5-dimethoxy-2-nitrobenzyl 8-bromo-cAMP (caged 8-Br-cAMP) (76) and 4,5-dimethoxy-2-nitrobenzyl 8-bromo-cGMP (caged 8-Br-cGMP) (77) by reaction of the respective cyclic... 

Cyclic Nucleotides.—New analogues of cAMP and cGMP that have been reported include 2-fluoroadenosine 3, 5 -monophosphate, 9-/ -D-xylofuranosylguanine 3, 5 -monophosphate, 8-carbamoyl- and 8-carboxy-adenosine 3, 5 -monophosphates (prepared from 8-bromo-cAMP, using standard transformations), and a series of 2-substituted-l,A -ethenoadenosine 3, 5 -monophosphates, prepared by ring reclosure of (30), which is the product of alkaline hydrolysis of 1, N -etheno-cAMP. The last-named have useful fluorescent properties, like the parent compound. So, also, have 8-azido-l,N -ethenoadenosine 3, 5 -monophosphate (also prepared... 

The PGE2-activated prostanoid receptors on DRG neurons (EPj, EP4, and some splice variants of EP3 receptors — EP3B and EP3( ) can be coupled to the stimulation of adenylate cyclase to raise cAMP levels. Experimental elevation of cAMP with the adenylate cyclase stimulator, forskolin, or application of membrane permeant cAMP analogues, dibutyryl cAMP (dbcAMP) and 8-bromo-cAMP, mimicked the effect of PGE2 treatment by shifting the activation... 

Certain proteins that appear to be present only in the synaptic plasmalem-ma have been shown to be phosphorylated specifically by cAMP-dependent kinase. Termed proteins la and Ib, these proteins are rapidly phosphorylated (in less than 5 sec) by electrical stimulation of presynaptic fibers and by application of the neurotransmitter believed to be released by the presynaptic neuron. Depolarizing agents, such as potassium and veratridine, when applied to the postsynaptic fibers, cause an enormous increase in the phosphorylation of proteins la and Ib. Dibutyryl cAMP and 8-bromo cAMP both mimic the actions of the neurotransmitters, as do phosphodiesterase inhibitors. The function of these proteins is at present unknown. 

Bromo-cAMP, cholera toxin MOF-7, ER-i- cancer cell line 3.3 X ... 

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