Cyclic Nucleotide Phosphodiesterases

Appleman, M. Michael; Ariano, Marjorie A.; Takemoto, Dolores J.; Whitson, Robert H.

doi:10.1007/978-3-642-68111-0_6

Cited by 36 publications

(28 citation statements)

References 163 publications

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“…MIX directly inhibits phosphodisterase, and thus cAMP is prevented from degrading into 5'AMP, whereas FOR activates adenyl cyclase used in converting ATP to CAMP. Use of these compounds as enhancers of cAMP was suggested by the MIX work of Appleman et al (1973) and the FOR work of Barovsky et al (1984), Seamon et al (1981), and Siegl et al (1982). The treated embryos were assessed to see if the neural tubes remained occluded and whether the levels of cytosol cAMP had changed.…”

Section: This Brings Up the Interesting Question Of How Ca2mentioning

confidence: 99%

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

Desmond

Duzy

Federici

1993

Developmental Dynamics

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We know that, once rostra1 neurulation is completed in the neuroaxis of the chick embryo, the caudal neurocoel becomes occluded and the brain rapidly expands. However, very little is known about the mechanisms maintaining occlusion. Studies had shown that occluded neurocoels reopened in embryos treated with chelators of cations, but the reasons remained unclear and the cations unidentified. To begin defining the role of cations, this study explored the effect of CaZC, calmodulin, and cAMP on maintaining the occluded neurocoel. Chick embryos during the natural phase of neurocoel occlusion (stage 12) were cultured in vitro with drugs known to modulate Ca2+ transport, to inhibit calmodulin activity, or to elevate cAMP levels. To test if occlusion is a Ca2+-dependent process, embryos were treated with verapamil and ionophore A23187. To test if occlusion requires calmodulin, embryos were treated with antipsychotic agents. To test if occlusion is cAMP dependent, embryos were treated with methylisobutylxanthine (MIX), forskolin (FOR), or dibutyl cyclic adenosine (DbC). Following each treatment, occlusion of the neurocoel was tested by injecting dye into the midbrain. All treatments resulted in a predominant number of precocious reopenings of the occluded neurocoels. MIX-treated, naked neural tubes had a fourfold increase in CAMP, whereas FOR-and DbCtreated neural tubes showed ten-and 14-fold increases, respectively. The presence of calmodulin in the cells of the neural tube was confirmed by fluorescent tagging and 3H-chlorpromazine labelling. The combined results of this study show that occlusion of the spinal neurocoel depends on exogenous Ca2+, requires calmodulin, and is cAMP sensitive. 0 1993 Wiley-Liss, Inc.

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Section: This Brings Up the Interesting Question Of How Ca2mentioning

confidence: 99%

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

Desmond

Duzy

Federici

1993

Developmental Dynamics

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“…These enzymes differ in their substrate specificities, kinetic characteristics, physical properties, and regulation (5)(6)(7). Most cells contain several of these forms of cyclic nucleotide phosphodiesterase but the role of each of these multiple species of phosphodiesterase in cells is still unclear.…”

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confidence: 99%

cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity.

Grant

Mannarino

Colman

1988

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

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Treatment of intact human platelets with the adenylate cyclase agonist forskolin (100 jbM) resulted in an increase in cAMP phosphodiesterase activity in freeze-thaw lysates. When the low-Km (high affinity), cGMP-inhibited cAMP phosphodiesterase was isolated from such lysates by blue dextran-Sepharose chromatography, the specific activity of the enzyme was increased an average of 11-fold over similarly processed control platelets. The increase in the low-K., cGMPinhibited cAMP phosphodiesterase activity was inhibited when platelets were incubated with the protein kinase inhibitor H-8 prior to treatment with forskolin, suggesting that the stimulation of cAMP phosphodiesterase activity involved a cAMPdependent phosphorylation. When intact platelets that had been prelabeled with 32p; were treated with forskolin and the low-K., cGMP-inhibited phosphodiesterase was isolated by blue dextran-Sepharose chromatography, a protein of 110,000 kDa was phosphorylated. By using a monospecific antiserum to the purified phosphodiesterase, this protein was shown to be the low-K., cGMP-inhibited cAMP phosphodiesterase by electrophoretic transfer blot (Western blot) analysis and by immunoprecipitation. The stable prostacyclin analog iloprost also stimulated the low-Km cAMP phosphodiesterase activity about 2-fold and caused phosphorylation of the enzyme. These results suggest that phosphorylation of the low-K., cGMP-inhibited phosphodiesterase may be an important regulatory mechanism for this enzyme in platelets.

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“…PDE plays a major role in the regulation of the intracellular concentrations of cAMP and cGMP (Appleman and Terasaki, 1975). PDEs are classified into several families (Beavo, 1995;Fawcett et al, 2000;Yuasa et al, 2000) and selective PDE inhibitors have been found (Beavo and Reifsnyder, 1990).…”

Section: Discussionmentioning

confidence: 99%

Lack of Cyclic Nucleotide Regulation of MBCQ-induced Relaxation of Rat Ileal Smooth Muscle.

Kaneda

Yamamoto

Azegami

et al. 2003

J. Smooth Muscle Res.

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The effects of the type V phosphodiesterase (PDE V) inhibitors, MBCQ, zaprinast and dipyridamole, on the relationship between relaxation and cyclic nucleotide content were investigated in rat ileal smooth muscle. Each of MBCQ (0.01-10 µM), zaprinast (0.1-100 µM) and dipyridamole (0.1-100 µM) inhibited carbachol (CCh; 10 µM)-induced contractions in a concentration-dependent manner. When compared with the concentrations of these agents producing 50% relaxation (IC50) of CCh-induced contraction, MBCQ was 14-20 fold more potent than the other agents. The inhibitory potency of these agents against high K + (65 mM KCl)-induced contractions were similar to that for CCh. MBCQ (1, 10 µM) did not significantly increase the cGMP content above control levels in the presence of CCh (10 µM). Both Zaprinast (1-100 µM) and dipyridamole (1-100 µM) increased the cGMP content of smooth muscle preparations in a concentration-dependent manner. There was a positive correlation between the inhibition of the CCh-induced contraction and the increase in cGMP content elicited by zaprinast and dipyridamole (zaprinast; r=0.72, P<0.05, dipyridamole; r=0.92, P<0.05). However, MBCQ at a concentration which induced a medium-sized relaxation did not significantly increase the cGMP content. Neither MBCQ, zaprinast nor dipyridamole significantly increased the cAMP content of the preparations above control. In summary, it is suggested that the inhibition of CCh-induced contractions by zaprinast and dipyridamole involves increases in cGMP content via inhibition of PDE V. However the inhibition of CCh-induced contraction by MBCQ may not involve cyclic nucleotides in rat ileal smooth muscle.

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Cyclic Nucleotide Phosphodiesterases

Cited by 36 publications

References 163 publications

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity.

Lack of Cyclic Nucleotide Regulation of MBCQ-induced Relaxation of Rat Ileal Smooth Muscle.

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