8-(4-Chlorophenyl)thio-cyclic AMP is a potent inhibitor of the cyclic GMP-specific phosphodiesterase (PDE VA)

Bj, Connolly; Pb, Willits; Bh, Warrington; Murray, Karen

doi:10.1016/0006-2952(92)90673-7

Cited by 28 publications

(11 citation statements)

References 13 publications

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“…The conclusion that the circadian phase shifts and acute stimulation of melatonin production observed in these studies resulted specifically from activation of cyclic AMP-dependent pathways is supported by the similarity in the effects of forskolin, IBMX, and 8-CPT-cAMP, which are structurally distinct and activate cyclic AMP pathways by different mechanisms (Seamon and Daly, 1986;Hoshi et al, 1988;Beavo and Reifsnyder, 1990;Stille and Stiles, 1991;Connolly et al, 1992). A specific action of forskolin through activation of adenylate cyclase is supported further by the lack of effects of 1‚9-dideoxyforskolin, which does not activate adenylate cyclase, but mimics nonspecific membrane effects of forskolin (Hoshi et al, 1988).…”

Section: Discussionmentioning

confidence: 86%

Cyclic AMP Resets the Circadian Clock in Cultured Xenopus Retinal Photoreceptor Layers

Hasegawa

Cahill

1998

Journal of Neurochemistry

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The Xenopus retinal photoreceptor layer contains a circadian oscillator that regulates melatonin synthesis in vitro. The phase of this oscillator can be reset by light or dopamine. The phase‐response curves for light and dopamine are similar, with transitions from phase delays to phase advances in the mid‐subjective night. Light and dopamine each can inhibit adenylate cyclase in retinal photoreceptors, suggesting cyclic AMP as a candidate second messenger for entrainment of the circadian oscillator. We report here that treatments that increase intracellular cyclic AMP reset the phase of the photoreceptor circadian oscillator, and that the phase‐response curves for these treatments are 180° out of phase with the phase‐response curves for light and dopamine. Activation of adenylate cyclase by forskolin during the late subjective day or early subjective night caused phase advances. The same treatment during the late subjective night or early subjective day caused phase delays. Similar phase shifts were induced by 3‐isobutyl‐1‐methyl‐xanthine (a phosphodiesterase inhibitor) or 8‐(4‐chlorophenylthio)cyclic AMP. All of these treatments also acutely increased melatonin release. Forskolin and 3‐isobutyl‐1‐methylxanthine increased the accumulation of intracellular cyclic AMP, but not cyclic GMP, in photoreceptor layers. The results indicate that cyclic AMP‐dependent pathways regulate the photoreceptor circadian oscillator and suggest that a decrease in cyclic AMP may be involved in circadian entrainment by light and/or dopamine.

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Section: Discussionmentioning

confidence: 86%

Cyclic AMP Resets the Circadian Clock in Cultured Xenopus Retinal Photoreceptor Layers

Hasegawa

Cahill

1998

Journal of Neurochemistry

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“…22 In addition, CPT-cAMP is highly membrane permeable because of its lipophilic C-8-substituent and unlike other analogues, such as 8-Br-cAMP, it can be hydrolyzed by cAMPspecific phosphodiesterase (PDE). A potential disadvantage of CPT-cAMP is that it is a competitive inhibitor of the cGMPspecific phosphodiesterase (PDE5a), 23 which may elevate intracellular cGMP levels. However, this may have had a minimal effect on our experiments, because the predominant PDE in photoreceptors is PDE6.…”

Section: Effect Of Cpt-camp On Photoreceptor Axon Terminal Retractionmentioning

confidence: 99%

Cyclic AMP Prevents Retraction of Axon Terminals in Photoreceptors Prepared for Transplantation: An In Vitro Study

Khodair

Zarbin

Townes‐Anderson

2005

Invest. Ophthalmol. Vis. Sci.

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“…Different concentrations of CPT-cAMP, a membrane-permeant cAMP analogue that is resistant to PDE [8], were applied to the bath. Figure 1A shows a representative recording from a cell-attached membrane patch that contains a few channels and thus yields microscopic current with identifiable single-channel opening and closing events.…”

Section: Concentration-dependent Activation Of Cftr By Cpt-campmentioning

confidence: 99%

Activation of wild-type and ΔF508-CFTR by phosphodiesterase inhibitors through cAMP-dependent and -independent mechanisms

Al‐Nakkash¹,

Hwang²

1999

Pfl�gers Archiv European Journal of Physiology

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The cAMP-dependent activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and its modulation through inhibition of phosphodiesterases (PDE) were studied with the cell-attached patch-clamp technique in Calu-3 cells (expressing endogenous CFTR) and NIH3T3 cells [expressing either wild-type (Wt)-CFTR or DeltaF508-CFTR]. In Calu-3 cells, CFTR current was augmented by increasing concentrations of 8-(4-chlorophenylthio)-adenosine 3', 5'-cyclic monophosphate (CPT-cAMP) and reached a saturating level at >/=60 microM. Varying the forskolin concentration also modulated CFTR activity; 10 microM was maximally effective since supplemental application of 200 microM CPT-cAMP had no additional effect. Activation of CFTR by increasing the cAMP concentration occurs through an increase of the NPo (product of the number of functional channels and the open probability) since the single-channel amplitude remains unchanged. In Calu-3 and NIH3T3-Wt cells, PDE inhibitors, milrinone (100 microM), 8-cyclopentyl-1, 3-dipropylxanthine (CPX, 25 microM), and 3-isobutyl-1-methylxanthine (IBMX, 200 microM), did not enhance CFTR current initially activated with 10 microM forskolin, but each potentiated CFTR activity elicited with a submaximal forskolin concentration (e.g., 100 nM) and prolonged the deactivation of CFTR channel current upon removal of forskolin. Millimolar IBMX increased the NPo of both Wt- and DeltaF508-CFTR even under maximal cAMP stimulation. Quantitatively, these effects of millimolar IBMX on NPo approximate those of genistein, which potentiates the cAMP-dependent CFTR activity via a mechanism that does not involve increases in cellular cAMP. Thus, depending on the concentration, PDE inhibitors may affect CFTR through different mechanisms.

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8-(4-Chlorophenyl)thio-cyclic AMP is a potent inhibitor of the cyclic GMP-specific phosphodiesterase (PDE VA)

Cited by 28 publications

References 13 publications

Cyclic AMP Resets the Circadian Clock in Cultured Xenopus Retinal Photoreceptor Layers

Cyclic AMP Resets the Circadian Clock in Cultured Xenopus Retinal Photoreceptor Layers

Cyclic AMP Prevents Retraction of Axon Terminals in Photoreceptors Prepared for Transplantation: An In Vitro Study

Activation of wild-type and ΔF508-CFTR by phosphodiesterase inhibitors through cAMP-dependent and -independent mechanisms

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