Selective inhibition of two soluble adenosine cyclic 3',5'-phosphate phosphodiesterases partially purified from calf liver

Yamamoto, Toshihiko; Lieberman, Ferol; Osborne, James C.; Manganiello, Vincent C.; Vaughan, Martha; Hidaka, Hiroyoshi

doi:10.1021/bi00299a013

Cited by 41 publications

(12 citation statements)

References 21 publications

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“…In the 1970s and 1980s, simple gel filtration and ion exchange chromatography of tissue extracts revealed multiple peaks of PDE activities, with each peak exhibiting different specificities and affinities for cGMP and/or cAMP as well as different sensitivities to available pharmacological agents and effectors such as calcium/calmodulin (the calcium/calmodulin-sensitive PDE is now known as PDE1) 22–26 . Consequently, drugs were successfully utilized to subdivide cAMP-hydrolysing PDEs into cilostamide-sensitive (now known as PDE3) and Ro20-1724-sensitive (now known as PDE4) enzymes 27 . Responsiveness to cGMP was also used to identify distinct PDEs: that is, cGMP-inhibited cAMP-hydrolysing PDEs (now known as PDE3) 25 , cGMP-stimulated cAMP-hydrolysing PDEs (now known as PDE2) 27 and cGMP-specific PDEs (now known as PDE5) 26 .…”

Section: History Of Pdes As Therapeutic Targetsmentioning

confidence: 99%

Advances in targeting cyclic nucleotide phosphodiesterases

Maurice

Ahmad

et al. 2014

Nat Rev Drug Discov

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667

766

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Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP and cyclic GMP, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signalling pathways and, consequently, myriad biological responses in health and disease. Currently, a small number of PDE inhibitors are used clinically for treating the pathophysiological dysregulation of cyclic nucleotide signalling in several disorders, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication and chronic obstructive pulmonary disease. However, pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual PDEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants.

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Section: History Of Pdes As Therapeutic Targetsmentioning

confidence: 99%

Advances in targeting cyclic nucleotide phosphodiesterases

Maurice

Ahmad

et al. 2014

Nat Rev Drug Discov

Self Cite

667

766

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“…Although there are a number of mechanisms by which cyclic GMP elevations could subsequently lead to rises in cyclic AMP, for example, activation by phosphorylation of adenylate cyclase by cyclic GMP-dependent protein kinase or inhibition of phosphodiesterase IV by cyclic GMP (Yamamoto et al, 1984), it is highly improbable that any of these mechanisms is responsible for the results presented above for a number of reasons. Firstly, acetylcholine at the concentration used, elevated cyclic GMP levels above those achieved by CGRP but did not cause any alterations in the levels of cyclic AMP.…”

Section: Time Course For Cyclic Nucleotide Accumulationmentioning

confidence: 99%

Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide

Gray

Marshall

1992

British J Pharmacology

139

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1 The signal transduction pathway for vasorelaxation induced by human a-calcitonin gene-related peptide (human a-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10-7 M). 2 Vasorelaxation by human a-CGRP was inhibited by haemogobin (10-6M) and methylene blue (10-5 M) but was unaffected by ibuprofen (10-5 M).3 Acetylcholine caused a 16 fold increase in levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) with levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) being unaltered. Human a-CGRP caused a 12 fold increase in levels of cyclic GMP but, in contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The rises in cyclic nucleotides evoked by human a-CGRP and acetylcholine were dependent on the presence of an intact endothelium. 4 N0-nitro-L-arginine (L-NOARG: 10-5 M), which inhibits nitric oxide synthase, inhibited the relaxant response to human a-CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation. 5 The data presented in this paper suggests that human a-CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human a-CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.

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“…The purified enzyme had a low Km (high affinity) for cAMP and was inhibited competitively by cGMP. Kinetically similar forms of phosphodiesterase activity have been described in a number of cell types (10)(11)(12)(13).…”

mentioning

confidence: 94%

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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Selective inhibition of two soluble adenosine cyclic 3',5'-phosphate phosphodiesterases partially purified from calf liver

Cited by 41 publications

References 21 publications

Advances in targeting cyclic nucleotide phosphodiesterases

Advances in targeting cyclic nucleotide phosphodiesterases

Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide

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

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