The novel distribution of phosphodiesterase-4 subtypes within the rat retina

Whitaker, Christopher J.; Cooper, Nigel G. F.

doi:10.1016/j.neuroscience.2009.07.045

Cited by 22 publications

(21 citation statements)

References 121 publications

(149 reference statements)

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“…Differential distribution of PDE proteins lead to compartmentalization of cAMP signaling (Houslay et al, 2007, Huston et al, 2008). We have previously reported that PDE4 proteins are differentially expressed within the retina (Whitaker and Cooper, 2007). Variable PDE distributions may provide a potential mechanism to segregate Epac signaling from PKA (Huston et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Anatomical studies of adenylate cyclase, the protein responsible for cAMP production, have revealed that 9 splice variants are present and differentially expressed throughout the retina (Abdel-Majid et al, 2002). Similarly, phosphodiesterases (PDEs), proteins responsible for hydrolyzing cyclic nucleotides, are expressed within the retina (Santone et al, 2006, Whitaker and Cooper, 2007). Thus, to better understand the function of cAMP within the retina, a focus on the distribution of functionally related proteins such as the exchange proteins directly-activated by cAMP is in order.…”

Section: Introductionmentioning

confidence: 99%

“…We have identified their relative distributions with the aid of double-labeling immunofluorescence with known retinal cell markers. Portions of these results have been presented in abstract form (Whitaker and Cooper, 2007 Whitaker and Cooper, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Differential distribution of exchange proteins directly activated by cyclic AMP within the adult rat retina

Whitaker

Cooper

2010

Neuroscience

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The recently discovered exchange protein directly activated by cAMP (Epac), a guanine exchange factor for the G-protein RAP-1, is directly activated by cAMP independently of PKA. While cAMP is known to be an important second messenger in the retina, the presence of Epac has not been investigated in this tissue. The goal of the present study was to determine if the Epac1 and Epac2 genes are present and to characterize their location within the retina. Western blot analysis revealed that Epac1 and Epac2 proteins are expressed within the retina, and the presence of mRNA was demonstrated with the aid of RT-PCR. Additionally, we used immunofluorescence and confocal microscopy to demonstrate that Epac1 and Epac2 have overlapping as well as unique distributions within the retina. Both are present within horizontal cells, rod and cone bipolar cells, cholinergic amacrine cells, retrograde labeled retinal ganglion cells, and Müller cells. Uniquely, Epac2 was expressed by cone photoreceptor inner and outer segments, cell bodies, and synaptic terminals. In contrast, Epac1 was expressed in VGlut1 and CtBP2 positive photoreceptor synaptic terminals. Together, these results provide evidence that Epac1 and Epac2 are differentially expressed within the retina and provide the framework for further functional studies of cAMP pathways within the retina.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential distribution of exchange proteins directly activated by cyclic AMP within the adult rat retina

Whitaker

Cooper

2010

Neuroscience

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“…Inhibition of PDE with IBMX enhanced the responses elicited by the diterpene activator of adenylyl cyclase, forskolin suggesting that catabolism of cyclic AMP does occur in these tissues. Indeed, there is evidence that PDE is present in several retinal cells such as the ganglion, bipolar, horizontal, amacrine and rod photoreceptors [32]. We included IBMX in all subsequent studies on the effects of H 2 S donors on cyclic AMP production in the retina.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hydrogen Sulfide on Cyclic AMP Production in Isolated Bovine and Porcine Neural Retinae

et al. 2009

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Hydrogen sulfide (H(2)S) has been reported to exert pharmacological effects on neural and non-neural tissues from several mammalian species. In the present study, we examined the role of the intracellular messenger, cyclic AMP in retinal response to H(2)S donors, sodium hydrosulfide (NaHS) and sodium sulfide (Na(2)S) in cows and pigs. Isolated bovine and porcine neural retinae were incubated in oxygenated Krebs buffer solution prior to exposure to varying concentrations of NaHS, Na(2)S or the diterpene activator of adenylate cyclase, forskolin. After incubation at different time intervals, tissue homogenates were prepared for cyclic AMP assay using a well established methodology. In isolated bovine and porcine retinae, the combination of both phosphodiesterase inhibitor, IBMX (2 mM) and forskolin (10 microM) produced a synergistic increase (P < 0.001) in cyclic AMP concentrations over basal levels. NaHS (10 nM-100 microM) produced a time-dependent increase in cyclic AMP concentrations over basal levels which reached a maximum at 20 min in both bovine and porcine retinae. At this time point, both NaHS and Na(2)S (10 nM-100 microM) caused a significant (P < 0.05) dose-dependent increase in cyclic AMP levels in bovine and porcine retinae. For instance, NaHS (100 nM) elicited a four-fold and three-fold increase in cyclic AMP concentrations in bovine and porcine retinae respectively whilst higher concentrations of Na(2)S (100 microM) produced a much lesser effect in both species. In bovine and porcine retinae, the effects caused by forskolin (10 microM) on cyclic AMP production were not potentiated by addition of low or high concentrations of both NaHS and Na(2)S. We conclude that H(2)S donors can increase cyclic AMP production in isolated neural retinae from cows and pigs. Bovine retina appears to be more sensitive to the stimulatory effect of H(2)S donors on cyclic nucleotide production than its porcine counterpart indicating that species differences exist in the magnitude of this response. Furthermore, effects produced by forskolin on cyclic AMP formation were not additive with those elicited by H(2)S donors suggesting that these agents may share a common mechanism in their action on the adenylyl cyclase pathway.

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“…2A). In double immunostaining, these DGKι-positive puncta were shown to be apposed side-by-side and never overlapped with immunoreactivity for vesicular glutamate transporter 1 (VGluT1), a marker for ribbon synapses of photoreceptor terminals in the OPL (Whitaker and Cooper 2009) (Fig. 2A,B).…”

Section: Dgkιmentioning

confidence: 99%

Distinct Expression and Localization of Diacylglycerol Kinase Isozymes in Rat Retina

Hozumi

Matsui

Sakane

et al. 2013

J Histochem Cytochem.

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Recent studies have revealed that phosphoinositide (PI) signaling molecules are expressed in mammalian retinas, suggesting their importance in its signal transduction. We previously showed that diacylglycerol kinase (DGK) isozymes are expressed in distinct patterns in rat retina at the mRNA level. However, little is known about the nature and morphological aspects of DGKs in the retina. For this study, we performed immunohistochemical analyses to investigate in the retina the expression and localization of DGK isozymes at the protein level. Here, we show that both DGKβ and DGKι localize in the outer plexiform layer, within which photoreceptor cells make contact with bipolar and horizontal cells. These isozymes exhibit distinct subcellular localization patterns: DGKι localizes to the synaptic area of bipolar cells in a punctate manner, whereas DGKβ distributes diffusely in the subsynaptic and dendritic regions of bipolar and horizontal cells. However, punctate labeling for DGKϵ is evident in the outer limiting membrane. DGKζ and DGKα localize predominantly to the nucleus of ganglion cells. These findings show distinct expression and localization of DGK isozymes in the retina, suggesting a different role of each isozyme.

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The novel distribution of phosphodiesterase-4 subtypes within the rat retina

Cited by 22 publications

References 121 publications

Differential distribution of exchange proteins directly activated by cyclic AMP within the adult rat retina

Differential distribution of exchange proteins directly activated by cyclic AMP within the adult rat retina

Effect of Hydrogen Sulfide on Cyclic AMP Production in Isolated Bovine and Porcine Neural Retinae

Distinct Expression and Localization of Diacylglycerol Kinase Isozymes in Rat Retina

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