Cardiotonic agents. 7. Inhibition of separated forms of cyclic nucleotide phosphodiesterase from guinea pig cardiac muscle by 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds. Structure-activity relationships and correlation with in vivo positive inotropic activity

1987 ◽  
Vol 30 (11) ◽  
pp. 1955-1962 ◽  
Author(s):  
Ila Sircar ◽  
Ronald E. Weishaar ◽  
Dianne Kobylarz ◽  
Walter H. Moos ◽  
James A. Bristol
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Cyclic Nucleotide ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Cardiotonic Agents ◽  
Structure Activity Relationships ◽  
Inotropic Activity ◽  
Structure Activity ◽  
Related Compounds

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.

Polybrominated dibenzo-p-dioxins and related compounds: Quantitative in vivo and in vitro structure-activity relationships

Toxicology ◽  
1987 ◽  
Vol 44 (3) ◽  
pp. 245-255 ◽  
Author(s):  
G. Mason ◽  
T. Zacharewski ◽  
M.A. Denomme ◽  
L. Safe ◽  
S. Safe
Keyword(s):  
Structure Activity Relationships ◽  
Structure Activity ◽  
Related Compounds

ChemInform Abstract: Structure-Activity Relationships of trans-3,5-Disubstituted Pyrrolidinylthio-1β-methylcarbapenems. Part 1. J-111,347 and Related Compounds.

ChemInform ◽  
2010 ◽  
Vol 31 (20) ◽  
pp. no-no
Author(s):  
Hideaki Imamura ◽  
Norikazu Ohtake ◽  
Aya Shimizu ◽  
Hideki Jona ◽  
Hiroki Sato ◽  
...  
Keyword(s):  
Structure Activity Relationships ◽  
Structure Activity ◽  
Abstract Structure ◽  
Related Compounds

Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure–activity relationships

2004 ◽  
Vol 68 (10) ◽  
pp. 2087-2094 ◽  
Author(s):  
Wun-Chang Ko ◽  
Chwen-Ming Shih ◽  
Ya-Hsin Lai ◽  
Jun-Hao Chen ◽  
Hui-Lin Huang
Keyword(s):  
Guinea Pig ◽  
Inhibitory Effects ◽  
Structure Activity Relationships ◽  
Structure Activity
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