Molecular cloning of cDNA encoding a “63”-kDa calmodulin-stimulated phosphodiesterase from bovine brain.

Bentley, J. Kelley; Kadlecek, A; Sherbert, C H; Seger, Dalia; Sonnenburg, William K.; Charbonneau, Harry; Novack, Jeffrey P.; Beavo, Joseph A.

doi:10.1016/s0021-9258(19)37014-0

Cited by 71 publications

(3 citation statements)

References 35 publications

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“…Within the AMPA‐induced cGMP responses, single PDE inhibition, especially of PDE1 and PDE2, but also of PDE3 elevated cGMP in both KOs. Both PDE1 and PDE2 have been previously identified to be highly expressed in the hippocampus (Beavo, 1995; Bentley et al, 1992; Kakkar et al, 1999; Polli & Kincaid, 1994; Russwurm et al, 2009). The impact of PDE1 inhibition was most pronounced in the NO‐GC1 KO indicating a special role of PDE1 in the degradation of NO‐GC2‐derived cGMP.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal AMPA‐ and NMDA‐induced cGMP signals are mainly generated by NO‐GC2 and are under tight control by PDEs 1 and 2

Giesen

Mergia

Koesling

et al. 2021

Eur J of Neuroscience

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In the central nervous system, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling cascade has an established role in fine‐tuning of synaptic transmission. In the present study, we asked which isoform of NO‐sensitive guanylyl cyclase, NO‐GC1 or NO‐GC2, is responsible for generation of N‐methyl‐d‐aspartate (NMDA)‐ and AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid)‐induced cGMP signals and which of the phosphodiesterases (PDEs) is responsible for degradation. To this end, we performed live cell fluorescence measurements of primary hippocampal neurons isolated from NO‐GC isoform‐deficient mice. Although both isoforms contributed to the NMDA‐ and AMPA‐induced cGMP signals, NO‐GC2 clearly played the predominant role. Whereas under PDE‐inhibiting conditions the cGMP levels elicited by both glutamatergic ligands were comparable, NMDA‐induced cGMP signals were clearly higher than the AMPA‐induced ones in the absence of PDE inhibitors. Thus, AMPA‐induced cGMP signals are more tightly controlled by PDE‐mediated degradation than NMDA‐induced signals. In addition, these findings are compatible with the existence of at least two different pools of cGMP in both of which PDE1 and PDE2—known to be highly expressed in the hippocampus—are mainly responsible for cGMP degradation. The finding that distinct pools of cGMP are equipped with different amounts of PDEs highlights the importance of PDEs for the shape of NO‐induced cGMP signals in the central nervous system.

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Section: Discussionmentioning

confidence: 99%

Hippocampal AMPA‐ and NMDA‐induced cGMP signals are mainly generated by NO‐GC2 and are under tight control by PDEs 1 and 2

Giesen

Mergia

Koesling

et al. 2021

Eur J of Neuroscience

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“…Despite the slight difference in the results, the two groups agreed on the fact that CaM-PDE activities are developmentally regulated in rodent germ cells. We need to wait 15 years until all PDE1 isoenzymes are cloned [58][59][60][61][62][63] before having a better characterization of the stage and cell-specific expression of PDE1 enzymes in murine testis [32]. A spatial and temporal expression pattern was observed for PDE1A and PDE1C, with PDE1B considered absent.…”

Section: Figurementioning

confidence: 99%

Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers

Campolo

Assenza

Venneri

et al. 2023

IJMS

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Phosphodiesterases are key regulators that fine tune the intracellular levels of cyclic nucleotides, given their ability to hydrolyze cAMP and cGMP. They are critical regulators of cAMP/cGMP-mediated signaling pathways, modulating their downstream biological effects such as gene expression, cell proliferation, cell-cycle regulation but also inflammation and metabolic function. Recently, mutations in PDE genes have been identified and linked to human genetic diseases and PDEs have been demonstrated to play a potential role in predisposition to several tumors, especially in cAMP-sensitive tissues. This review summarizes the current knowledge and most relevant findings regarding the expression and regulation of PDE families in the testis focusing on PDEs role in testicular cancer development.

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“…Compared with other PDEs, PDE‐1 is specifically regulated by the Ca 2+ /calmodulin signalling pathway 9,10 . PDE‐1 also has 3 gene expressions, PDE1A, PDE1B and PDE1C, which was found to be abundant in the heart and brain 9,11 .…”

Section: Introductionmentioning

confidence: 99%

Effects of phosphodiesterase‐1 inhibitor on pulmonary vein electrophysiology and arrhythmogenesis

Yugo

Chen

Lin

et al. 2021

Eur J Clin Investigation

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Introduction: Phosphodiesterase (PDE) isoform inhibitors have mechanical and electrical effects on the heart. Inhibition of PDE-1 enzymes is a novel strategy for treating heart failure. However, the electrophysiological effects of PDE-1 inhibition on the heart remain unclear. This study explored the effects of PDE-1 inhibition using ITI-214 on electrical activity in the pulmonary vein (PV), the most common trigger of atrial fibrillation, and investigated the underlying ionic mechanisms. Methods: Conventional microelectrodes or whole-cell patch clamps were employed to study the effects of ITI-214 (0.1-10 μM) on PV electrical activity, mechanical responses and ionic currents in isolated rabbit PV tissue specimens and isolated single PV cardiomyocytes. Results: ITI-214 at 1 μM and 10 μM (but not 0.1 μM) significantly reduced PV spontaneous beating rate (10 ± 2% and 10 ± 3%, respectively) and PV diastolic tension (11 ± 3% and 17 ± 3%, respectively). ITI-24 (1 μM) significantly reduced late sodium current (I Na-Late ), L-type calcium current (I Ca-L ) and the reverse mode of the sodium-calcium exchanger (NCX), but it did not affect peak sodium currents. Conclusions: ITI-214 reduces PV spontaneous activity and PV diastolic tension by reducing I Na-Late , I Ca-L and NCX current. Considering its therapeutic potential in heart failure, targeting PDE-1 inhibition may provide a novel strategy for managing atrial arrhythmogenesis.

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Molecular cloning of cDNA encoding a “63”-kDa calmodulin-stimulated phosphodiesterase from bovine brain.

Cited by 71 publications

References 35 publications

Hippocampal AMPA‐ and NMDA‐induced cGMP signals are mainly generated by NO‐GC2 and are under tight control by PDEs 1 and 2

Hippocampal AMPA‐ and NMDA‐induced cGMP signals are mainly generated by NO‐GC2 and are under tight control by PDEs 1 and 2

Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers

Effects of phosphodiesterase‐1 inhibitor on pulmonary vein electrophysiology and arrhythmogenesis

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