Increased Levels of 3′,5′‐Cyclic Adenosine Monophosphate Induced by Cobaltous Ion or 3‐Isobutylmethylxanthine in the Incubated Mouse Retina: Evidence Concerning Location and Response to Ions and Light

Cohen, Adolph I.

doi:10.1111/j.1471-4159.1982.tb08699.x

Cited by 36 publications

(24 citation statements)

References 57 publications

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“…We included 1 mM IMBX in the incubation medium for two reasons. However, if IBMX is included in the medium (Cohen, 1982;Cohen & Blazynski, 1987), the cAMP levels of DKA-DI and LA-LI retinas both increase, but the cAMP of LI retinas plateaus at 1-2 min while that of the DI retinas continues to increase and at 6 min in IBMX medium is ca. Secondly, as shown in our earlier studies (Mitzel et al, 1978), when LA mouse retinas are incubated in Earle's medium in the light (LA-LI), there is a transient elevation in cAMP that peaks at 5-6 min and matches the cAMP level of dark-adapted, dark-incubated (DKA-DI) retinas, followed by a decline to a stable level well below that of DKA-DI retinas.…”

Section: Resultsmentioning

confidence: 96%

“…Quantitative determinations of cyclic AMP in vertebrate photoreceptors have been reported (DeVries et al, 1978;Ferrendelli et al, 1980;Cohen, 1982;Blazynski & Cohen, 1984), but the various functions subserved by this molecule in these cells are not well-defined. In some amphibians, cyclic AMP levels in photoreceptors have been shown to influence the shedding of the membranous disks of rod outer segments (Besharse et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

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Dopamine and its agonists reduce a light-sensitive poor of cyclic AMP in mouse photoreceptors

Cohen

Blazynski

1990

Vis Neurosci

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The exposure to bright light of dark-adapted (DKA) mouse retinas incubated in the dark (DI) in IBMX-containing medium causes a marked loss of cyclic AMP. This light response also occurs if the medium contains 10 mM aspartate or cobaltous ion, agents believed to confine the effects of light to photoreceptors. Thus, the action of light in the presence of either of these agents defines a light-sensitive pool of cyclic AMP in photoreceptors. This pool could also be reduced or eliminated in DKA-DI retinas by nanomolar to micromolar levels of dopamine (if the medium contained SCH23390, a potent antagonist of Dl receptors), thus indicating an agonistic action of dopamine at D2 receptors. The D2 agonists LY171555 (EC 50 10 nM) or (+)-3-PPP also reduced the cyclic AMP level in the dark. Of the D2 antagonists tested, the butyrophenone spiperone (in the presence of the 5HT-2 blocker ketanserin) countered the action of the D2 agonists but substituted benzamides were ineffective. Consistently, the D2 agonists had no effect on cyclic AMP levels of mutant retinas lacking photoreceptors (rd/rd), but reduced cyclic AMP in DKA-DI glutamate-modified retinas which exhibit a major loss of inner retinal neurons without apparent loss of photoreceptors. The Dl antagonist SCH23390 only reduced cyclic AMP levels of DKA-DI retinas when cyclic AMP levels had been elevated by adding dopamine to the incubation medium.

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Dopamine and its agonists reduce a light-sensitive poor of cyclic AMP in mouse photoreceptors

Cohen

Blazynski

1990

Vis Neurosci

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“…Therefore, these proteins may be regulated by light-dependent changes in cAMP levels, which are well documented in vertebrate photoreceptor cells (12,13,15,61). Calmodulin (CaM), activated by higher Ca 2ϩ concentrations in the dark, stimulates cAMP synthesis by adenylyl cyclase Type I (AC1) (12,14,62,63). Both phosducin and RGS9 -1 demonstrate increased phosphorylation in the dark, consistent with the higher levels of cAMP in photoreceptor cells observed under these conditions (25,48), although recent work on phosducin suggests that higher cAMP in the dark may not always involve regulation by Ca 2ϩ (35).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of GRK1 and GRK7 by cAMP-dependent Protein Kinase Attenuates Their Enzymatic Activities

Horner¹,

Osawa²,

Schaller

et al. 2005

Journal of Biological Chemistry

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Phosphorylation of G protein-coupled receptors is a critical step in the rapid termination of G protein signaling. In rod cells of the vertebrate retina, phosphorylation of rhodopsin is mediated by GRK1. In cone cells, either GRK1, GRK7, or both, depending on the species, are speculated to initiate signal termination by phosphorylating the cone opsins. To compare the biochemical properties of GRK1 and GRK7, we measured the K m and V max of these kinases for ATP and rhodopsin, a model substrate. The results demonstrated that these kinases share similar kinetic properties. We also determined that cAMP-dependent protein kinase (PKA) phosphorylates GRK1 at Ser 21 and GRK7 at Ser 23 and Ser 36 in vitro. These sites are also phosphorylated when FLAGtagged GRK1 and GRK7 are expressed in HEK-293 cells treated with forskolin to stimulate the endogenous production of cAMP and activation of PKA. Rod outer segments isolated from bovine retina phosphorylated the FLAG-tagged GRKs in the presence of dibutyryl-cAMP, suggesting that GRK1 and GRK7 are physiologically relevant substrates. Although both GRKs also contain putative phosphorylation sites for PKC and Ca 2؉ /calmodulin-dependent protein kinase II, neither kinase phosphorylated GRK1 or GRK7. Phosphorylation of GRK1 and GRK7 by PKA reduces the ability of GRK1 and GRK7 to phosphorylate rhodopsin in vitro. Since exposure to light causes a decrease in cAMP levels in rod cells, we propose that phosphorylation of GRK1 and GRK7 by PKA occurs in the dark, when cAMP levels in photoreceptor cells are elevated, and represents a novel mechanism for regulating the activities of these kinases. G protein-coupled receptors (GPCRs)1 belong to the largest family of signal-transducing proteins in eukaryotes. They mediate cellular responses to a variety of environment stimuli, including light, taste, odorants, ions, nucleotides, peptides, and lipids, through the activation of heterotrimeric G proteins (1-4). Phosphorylation of ligand-activated GPCRs by G proteincoupled receptor kinases (GRKs) is the initial step in the rapid termination or desensitization of GPCR signal transduction. For example, in rod cells of the vertebrate retina, desensitization occurs when light-activated rhodopsin is phosphorylated by GRK1, followed by the binding of visual arrestin to the phosphorylated rhodopsin, which blocks its interaction with transducin, the rod cell G protein (5). Although desensitization also occurs in cone cells, less is known about the proteins involved and their regulation. GRK1 and a cone-specific GRK, GRK7, are coexpressed in human and monkey cone cells (6 -8) where both may contribute to the deactivation of cone opsins (7-9). In contrast, only GRK7 is expressed in the cones of pigs and dogs. However, it is absent from the mouse genome altogether and mouse cones express only GRK1 (7). Therefore, differences in cone visual transduction between species may result in part from variations in the expression pattern of GRK1 and GRK7. We recently implicated GRK7 in the phosphorylation of cone o...

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“…Photoreceptor cAMP is regulated by light exposure, which decreases levels of the second messenger (Orr et al, 1976;DeVries et al, 1978;Cohen, 1982). In photoreceptor-enriched chick retinal cell cultures, light treatment at night dramatically decreased the cAMP levels and AANAT activity, and the effects of light on AANAT activity were reversed by incubating the cells with 8Br-cAMP or lactacystin (Ivanova and Iuvone, 2003).…”

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confidence: 99%

Photic Regulation of ArylalkylamineN-Acetyltransferase Binding to 14-3-3 Proteins in Retinal Photoreceptor Cells

Pozdeyev¹,

Taylor²,

Haque³

et al. 2006

J. Neurosci.

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14-3-3 proteins are a ubiquitous, highly conserved family of chaperone proteins involved in signal transduction, regulation of cell cycle, intracellular trafficking/targeting, cytoskeletal structure, and transcription. Although 14-3-3 proteins are among the most abundant proteins in the CNS, very little is known about their functional roles in the vertebrate retina. In the present study, we demonstrated that photoreceptors express 14-3-3 protein(s) and identified a 14-3-3 binding partner in photoreceptor cells, the melatonin-synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT). Importantly, our data demonstrate that the binding of 14-3-3 to AANAT is regulated by light, with dramatic functional consequences. During the night in darkness, retinal AANAT is phosphorylated and forms a complex with 14-3-3 proteins with an apparent molecular weight of ϳ90 kDa. Phosphorylation of AANAT facilitates the binding of enzyme to 14-3-3 proteins. Within the complex, AANAT is catalytically activated and protected from dephosphorylation and degradation. Light disrupts the AANAT/14-3-3 complex, leading to catalytic inactivation, dephosphorylation, and proteolytic degradation of the enzyme. In the presence of the proteasome inhibitor, lactacystin, light results in the formation of a high molecular weight complex (Ͼ150 kDa), which may represent an intermediate in the AANAT degradation process. These findings provide new insight into the roles of 14-3-3 proteins in photoreceptor cells and to the mechanisms controlling melatonin synthesis in the vertebrate retina.

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Increased Levels of 3′,5′‐Cyclic Adenosine Monophosphate Induced by Cobaltous Ion or 3‐Isobutylmethylxanthine in the Incubated Mouse Retina: Evidence Concerning Location and Response to Ions and Light

Cited by 36 publications

References 57 publications

Dopamine and its agonists reduce a light-sensitive poor of cyclic AMP in mouse photoreceptors

Dopamine and its agonists reduce a light-sensitive poor of cyclic AMP in mouse photoreceptors

Phosphorylation of GRK1 and GRK7 by cAMP-dependent Protein Kinase Attenuates Their Enzymatic Activities

Photic Regulation of ArylalkylamineN-Acetyltransferase Binding to 14-3-3 Proteins in Retinal Photoreceptor Cells

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