Signal tranduction: regulation of cAMP concentration in cardiac muscle by calmodulin-dependent cyclic nucleotide phosphodiesterase

1995 ◽  
Vol 149-150 (1) ◽  
pp. 241-247 ◽  
Author(s):  
Rajendra K. Sharma
Keyword(s):  
Cardiac Muscle ◽  
Cyclic Nucleotide ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Camp Concentration ◽  
Signal Tranduction

Regulation of cAMP concentration by calmodulin-dependent cyclic nucleotide phosphodiesterase

1986 ◽  
Vol 64 (11) ◽  
pp. 1072-1080 ◽  
Author(s):  
Rajendra K. Sharma ◽  
Jerry H. Wang
Keyword(s):  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Bovine Brain ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Camp Concentration ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Molecular Masses ◽  
Regulatory Properties

Bovine brain contains two major calmodulin (CaM) dependent phosphodiesterase isozymes which are homodimeric proteins with subunit molecular masses of 60 and 63 kilodaltons (kDa), respectively. The 60-kDa subunit isozyme can be phosphorylated by cAMP-dependent protein kinase, resulting in a decrease in the enzyme affinity towards CaM. The phosphorylation is blocked by Ca2+ and CaM and reversed by the CaM-stimulated phosphatase (calcineurin). The 63-kDa subunit isozymes can also be phosphorylated, but in this case by a CaM-dependent protein kinase(s). This phosphorylation is also accompanied by a decrease in the isozyme affinity towards CaM and can be reversed by the CaM-dependent phosphatase. Analysis of the complex regulatory properties of the phosphodiesterase isozymes has led to the suggestion that fluxes of cAMP and Ca2+ during cell activations are closely coupled and that the CaM-dependent phosphodiesterase isozymes play key roles in this signal coupling phenomenon.

scholarly journals KS-505a, an isoform-selective inhibitor of calmodulin-dependent cyclic nucleotide phosphodiesterase

1996 ◽  
Vol 316 (1) ◽  
pp. 311-316 ◽  
Author(s):  
Michio ICHIMURA ◽  
Rika EIKI ◽  
Keiko OSAWA ◽  
Satoshi NAKANISHI ◽  
Hiroshi KASE
Keyword(s):  
Cyclic Nucleotide ◽  
Hippocampal Slices ◽  
Selective Inhibitor ◽  
Binding Domain ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Intracellular Camp ◽  
Camp Concentration ◽  
Striatal Slices

The effects of KS-505a, a novel microbial metabolite, on the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE) were investigated. (1) KS-505a potently inhibited the purified 61 kDa isoenzyme of CaM-PDE from bovine brain and required much higher doses to inhibit the purified 59 kDa isoenzyme of CaM-PDE from bovine heart. The inhibition of both isoenzymes was observed only in the presence of calcium-activated calmodulin (Ca2+/CaM). The IC50 values for the 61 and 59 kDa isoenzymes were 0.17 and 13 μM respectively with 20 μM cAMP as a substrate. (2) Kinetic analysis indicated that the inhibitory mode of KS-505a for the 61 kDa isoenzyme was competitive with respect to Ca2+/CaM; the Ki for KS-505a was 0.089 μM. The inhibition was not competitive with respect to the substrates cAMP or cGMP. (3) KS-505a did not interfere with the interaction between Ca2+/CaM and n-phenyl-1-naphthylamine, a hydrophobic fluorescent probe, nor was it adsorbed to CaM-conjugated gels in the presence of Ca2+, thereby indicating that KS-505a does not bind to Ca2+/CaM. (4) Trypsin-activated 61 kDa isoenzyme, which lacked the Ca2+/CaM-binding domain, was not inhibited by KS-505a at less than micromolar concentrations. Taken together, these results suggest that KS-505a apparently bound to a site in the Ca2+/CaM-binding domain of the 61 kDa isoenzyme and selectively inhibited Ca2+/CaM-activated 61 kDa isoenzyme activity. (5) In rat hippocampal slices, KS-505a at 10 μM increased the intracellular cAMP concentration to approximately three times the basal level, whereas in rat striatal slices it had no effect on the cAMP concentration at concentrations of 1.0–10 μM, suggesting that each CaM-PDE isoenzyme functions differentially in these regions. These results demonstrate that KS-505a is a highly potent selective inhibitor both in vitro and in vivo and distinguishes between subfamily members within the CaM-PDE family.

scholarly journals The identification of a new cyclic nucleotide phosphodiesterase activity in human and guinea-pig cardiac ventricle. Implications for the mechanism of action of selective phosphodiesterase inhibitors

1987 ◽  
Vol 241 (2) ◽  
pp. 535-541 ◽  
Author(s):  
M L Reeves ◽  
B K Leigh ◽  
P J England
Keyword(s):  
Cyclic Amp ◽  
Guinea Pig ◽  
Cardiac Muscle ◽  
Cyclic Gmp ◽  
Cyclic Nucleotide ◽  
Gel Filtration ◽  
Phosphodiesterase Inhibitors ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Kinetic Properties ◽  
Cardiac Ventricle

Four cyclic nucleotide phosphodiesterase (PDE) activities were separated from low-speed supernatants of homogenates of human cardiac ventricle by DEAE-Sepharose chromatography, and designated PDE I-PDE IV in order of elution with an increasing salt gradient. PDE I was a Ca2+/calmodulin-stimulated activity, and PDE II was an activity with a high Km for cyclic AMP which was stimulated by low concentrations of cyclic GMP. Human ventricle PDE III had Km values of 0.14 microM (cyclic AMP) and 4 microM (cyclic GMP), and showed simple Michaelis-Menten kinetics with both substrates. PDE IV is a previously unrecognized activity in cardiac muscle, the human enzyme having Km values of 2 microM (cyclic AMP) and 50 microM (cyclic GMP). PDE III and PDE IV were not activated by cyclic nucleotides or calmodulin. Four PDE activities were also isolated from guinea-pig ventricle, and had very similar kinetic properties. By gel filtration, the Mr of PDE III was 60,000, and that of PDE IV 45,000. The drug SK&F 94120 selectively and competitively inhibited PDE III with a Ki value of 0.8 microM (human), showing simple hyperbolic inhibition kinetics. Rolipram (Schering ZK 62711) and Ro 20-1724 (Roche), which have previously been reported to inhibit PDE III-like activities strongly, were shown to be weak inhibitors of human and guinea-pig PDE III enzymes (Ki values greater than 25 microM), but potent inhibitors of PDE IV [Ki values 2.4 microM (Rolipram) and 3.1 microM (Ro 20-1724) with human PDE IV]. The inhibition in all cases demonstrated simple hyperbolic competition. These observations suggest that the previously reported complex inhibition of PDE III-type activities from cardiac muscle was caused by incomplete separation of the PDE III from other enzymes, particularly PDE IV.

Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) splice variants from bovine cardiac muscle

Gene ◽  
2007 ◽  
Vol 396 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Shankar B. Das ◽  
Chris Dinh ◽  
Sachin Shah ◽  
Doug Olson ◽  
Andrew Ross ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Cyclic Nucleotide ◽  
Splice Variants ◽  
Cyclic Nucleotide Phosphodiesterase

Differential pharmacologic sensitivity of cyclic nucleotide phosphodiesterase isozymes isolated from cardiac muscle, arterial and airway smooth muscle

1988 ◽  
Vol 150 (1-2) ◽  
pp. 85-94 ◽  
Author(s):  
Paul J. Silver ◽  
Linda T. Hamel ◽  
Mark H. Perrone ◽  
Ross G. Bentley ◽  
Cynthia R. Bushover ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cardiac Muscle ◽  
Airway Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Cyclic Nucleotide Phosphodiesterase

194: Influence of the Inhibition of Cyclic Nucleotide Phosphodiesterase type 4 on Human Detrusor Smooth Muscle Contractions

2006 ◽  
Vol 175 (4S) ◽  
pp. 63-63 ◽  
Author(s):  
Stephanie Oger ◽  
Delphine Behr-Roussel ◽  
Jacques Bernabe ◽  
Pierre Denys ◽  
Eva Camperat ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Muscle Contractions ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Detrusor Smooth Muscle ◽  
Phosphodiesterase Type ◽  
Smooth Muscle Contractions ◽  
Human Detrusor
Sign in / Sign up

Export Citation Format

Share Document