Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs)

Juilfs, Dawn M.; Soderling, Scott H.; Burns, Fiona; Beavo, Joseph A.

doi:10.1007/bfb0033670

Cited by 130 publications

(95 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The anti-PDE5 antibody showed the presence of PDE5 protein at least in the first, second, and third branches of dendrites of Purkinje cells, although in situ hybridization analysis in our previous studies could not reveal the intracellular localization of PDE5 protein. Recently, similar results from another group have been reported in mouse cerebellum (Juilfs et al 1999). Therefore, PDE5 may be important in degradating cGMP as soon as cGMP generates near each synapse by the stimulation of parallel fibers, and the presence of PDE5 in the dendrites may be attributed to cGMP signaling for the induction of local long-term depression between specific synapses.…”

Section: Discussionsupporting

confidence: 74%

Immunohistochemical Localization of cGMP-binding cGMP-specific Phosphodiesterase (PDE5) in Rat Tissues

Kotera

Fujishige

Omori

2000

J Histochem Cytochem.

109

View full text Add to dashboard Cite

S U M M A R YWe raised a polyclonal antibody against maltose binding protein fusion human cGMP-binding, cGMP-specific phosphodiesterase (PDE5) produced in E. coli. This antibody immunoreacted specifically with recombinant human and rat PDE5 proteins expressed in transfected COS-7 cells and with a native form of PDE5 in extracts of rat platelets, lung, and cerebellum. Immunohistochemical analysis showed that the anti-PDE5 antibody detected immunoactive materials in Purkinje cell layers of the cerebellum, proximal renal tubules, collecting renal ducts, and epithelial cells of pancreatic ducts in rats. Reverse transcriptase-polymerase chain reaction analysis demonstrated that PDE5 transcripts are also present in rat cerebellum, kidney, and pancreas. Here we described a cell-specific localization of PDE5 in various rat tissues, suggesting the possibility of the presence of a cGMP/PDE5 pathway in these tissues.

show abstract

Section: Discussionsupporting

confidence: 74%

Immunohistochemical Localization of cGMP-binding cGMP-specific Phosphodiesterase (PDE5) in Rat Tissues

Kotera

Fujishige

Omori

2000

J Histochem Cytochem.

109

View full text Add to dashboard Cite

show abstract

“…Accordingly, the cGMP response in the striatal neurons was an intermediate, triphasic shape resembling that seen in platelets incubated with 1 M sildenafil. In the striatal neurons, the main isoform at work is PDE2 rather than PDE5, but PDE2 activity is also enhanced when cGMP binds to a GAF domain (35), and the published data can be modeled more faithfully by assuming a PDE activity that augments with time (result not shown), rather than by one with the static Michaelis-Menten parameters used beforehand (13).…”

Section: Differential Potency Of No For Gc-coupled Receptors In Cellsmentioning

confidence: 99%

Kinetics of a Cellular Nitric Oxide/cGMP/Phosphodiesterase-5 Pathway

Amin

Bianco³

et al. 2004

Journal of Biological Chemistry

103

View full text Add to dashboard Cite

Rat platelets served as a model to evaluate quantitatively how guanylate cyclase (GC)-coupled nitric oxide (NO) receptors and phosphodiesterases (here phosphodiesterase-5) interact to transduce NO signals in cells. The platelets expressed mRNA only for the ␣ 1 and ␤ 1 GC-coupled receptor subunits. In intact platelets, the potency of NO for elevating cGMP (EC 50 ‫؍‬ 10 nM) was lower than in lysed platelets (EC 50 ‫؍‬ 1.7 nM). The limiting activities of GC and phosphodiesterase in intact platelets were both very high, being equivalent to about 100 M/s. With low phosphodiesterase activity (imposed by 100 M sildenafil), the cGMP response over time was hyperbolic in shape for a range of NO concentrations or GC activities due to GC desensitization. Without a phosphodiesterase inhibitor, NO generated only brief cGMP transients, peaking after 2-5 s but amounting maximally to about 150 M cGMP. The transients were caused partly by GC desensitization, which varied in rate (halftime up to 3 s) and extent (up to 80%) depending on the NO concentration, and partly by an enhancement of the phosphodiesterase catalytic activity with time, which was deduced to be up to 30-fold and to occur with a half-time of up to 5 s. The results were simulated by a quantitative model, which also explains the varied shapes of cGMP responses to NO found in other cells. Downstream phosphorylation in platelets was detectable within 2 s, and, with continuous exposure (1 min), this pathway could be engaged by subnanomolar NO concentrations (EC 50 ‫؍‬ 0.5 nM).Whereas the spatio-temporal dynamics of some of the primary steps of cellular signal transduction, such as synaptic transmission and changes in intracellular Ca 2ϩ , have become well understood in quantitative terms (1, 2), knowledge of downstream signaling cascades remains largely qualitative. Nevertheless, the kinetic properties of the second messenger cascades are likely to be similarly instrumental in determining how cells respond.A case in point is nitric oxide (NO) 1 signaling. NO acts as a diffusible chemical messenger throughout the body, where it subserves diverse functions, including smooth muscle relaxation, inhibition of platelet aggregation, and the induction of synaptic plasticity (3,4). NO elicits these and other physiological effects by binding to its guanylyl cyclase (GC)-coupled receptors, thereby evoking the accumulation of cGMP in target cells. The receptors are ␣␤-heterodimers, of which two main isoforms, ␣ 1 ␤ 1 and ␣ 2 ␤ 1 , exist at differing levels in different tissues (5). Studies on purified receptors (6) and intact cells (7) suggest that activation of GC occurs very rapidly, within a few ms or less of adding NO, and complete deactivation in cells (upon removal of NO) requires only about 500 ms (7). Furthermore, when studied in isolation, the receptors are highly sensitive NO detectors, with only about 1 nM being needed to evoke half-maximal GC activity (8). The shape of the resulting cGMP response in cells, however, varies greatly from one cell to another. For example,...

show abstract

“…Eleven different PDE gene families have been described and characterized based on their sequences and regulatory properties (6)(7)(8). Recent work has described changes in the expression of several PDE isoforms in monocytes and monocyte-derived cells upon cytokine stimulation (9)(10)(11).…”

mentioning

confidence: 99%

PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte

Bender

Beavo

2006

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

View full text Add to dashboard Cite

Monocyte-to-macrophage differentiation with the cytokine granulocyte-macrophage colony-stimulating factor induces expression of the cyclic nucleotide phosphodiesterase PDE1B2. However, what role PDE1B2 plays in macrophage biology has not been elucidated. We have addressed this question by inhibiting PDE1B2 induction by using RNA interference. Using a retrovirus-based system, we created HL-60 stable cell lines that express a short-hairpin RNA targeting PDE1B2. HL-60 cells treated with phorbol-12-myristate-13-acetate differentiate to a macrophage-like phenotype and upregulate PDE1B2. However, expression of PDE1B2 short hairpin RNA effectively suppresses PDE1B2 mRNA, protein, and activity up-regulation. Using the HL-60 PDE1B2 knockdown cells and agonists for either adenylyl or guanylyl cyclase, it was found that PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists. Furthermore, in intact HL-60 cells, PDE1B2 activity can be regulated by changes in Ca ؉2 levels. Inhibiting PDE1B2 up-regulation does not prevent HL-60 cell differentiation, because several markers of macrophage differentiation are unaffected. However, suppression of PDE1B2 expression alters some aspects of the macrophage-like phenotype, because cell spreading, phagocytic ability, and CD11b expression are augmented. The cAMP analog 8-Bromo-cAMP reverses the changes caused by PDE1B2 knockdown. Also, PDE1B2 knockdown cells have lower basal levels of cAMP and alterations in the phosphorylation state of several probable PKA substrate proteins. Thus, the effects of PDE1B2 on differentiation may ultimately be mediated through decreased cAMP. In conclusion, PDE1B2 regulates a subset of phenotypic changes that occur upon phorbol-12-myristate-13-acetate-induced differentiation and likely also plays a role in differentiated macrophages by regulating agonist-stimulated cGMP levels.cyclic AMP ͉ cyclic GMP ͉ phosphodiesterase

show abstract

Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs)

Cited by 130 publications

References 109 publications

Immunohistochemical Localization of cGMP-binding cGMP-specific Phosphodiesterase (PDE5) in Rat Tissues

Immunohistochemical Localization of cGMP-binding cGMP-specific Phosphodiesterase (PDE5) in Rat Tissues

Kinetics of a Cellular Nitric Oxide/cGMP/Phosphodiesterase-5 Pathway

PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte

Contact Info

Product

Resources

About