Selective inhibitory effect of new phosphodiesterase inhibitors on PDE isozymes in guinea pig cardiac muscle

1989 ◽  
Vol 12 (4) ◽  
pp. 276-281 ◽  
Author(s):  
Sun Kyeong Lee ◽  
Kwang Il Kwon ◽  
Ok Pyo Zee
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect

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.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 804-809 ◽  
Author(s):  
Torstein Lyberg
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Immune Complexes ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect ◽  
Intracellular Camp ◽  
Human Monocytes ◽  
Purified Protein Derivative ◽  
A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

scholarly journals Effects of an unprecedented polypeptide polytheonamide B isolated from marine sponge on the guinea-pig cardiac muscle.

1996 ◽  
Vol 71 ◽  
pp. 313
Author(s):  
Matomo Nishio ◽  
Nobuhiro Fusetani ◽  
Shigeki Matsunaga ◽  
Ikunohu Muramatsu
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Marine Sponge

scholarly journals Inhibitory effect of beauvericin on a high K+-induced tonic contraction in guinea-pig taenia coli.

1987 ◽  
Vol 45 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Shinjiro NAKAJYO ◽  
Kiyomi MATSUOKA ◽  
Tomohiro KITAYAMA ◽  
Yutaka YAMAMURA ◽  
Kazumasa SHIMIZU ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Inhibitory Effect ◽  
Tonic Contraction ◽  
Taenia Coli ◽  
High K

scholarly journals Evidence for the regulation of guinea-pig heart microsomal phosphatidylcholine-hydrolysing phospholipase A1 by guanosine 5′-[γ-thio]triphosphate

1992 ◽  
Vol 288 (3) ◽  
pp. 965-968 ◽  
Author(s):  
K Badiani ◽  
X Lu ◽  
G Arthur
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Guinea Pig ◽  
Molecular Species ◽  
Inhibitory Effect ◽  
Phospholipase A1 ◽  
Guinea Pig Heart ◽  
Substrate Specificities ◽  
Rate Of Hydrolysis ◽  
Hydrolysis Of

We have recently characterized lysophospholipase A2 activities in guinea-pig heart microsomes and postulated that these enzymes act sequentially with phospholipases A1 to release fatty acids selectively from phosphatidylcholine (PC) and phosphatidylethanolamine, thus providing an alternative route to the phospholipase A2 mode of release. In a further investigation of the postulated pathway, we have characterized the PC-hydrolysing phospholipase A1 in guinea-pig heart microsomes. Our results show that the enzyme may have a preference for substrates with C16:0 over C18:0 at the sn-1 position. In addition, although the enzyme cleaves the sn-1 fatty acid, the rate of hydrolysis of PC substrates with C16:0 at the sn-1 position was influenced by the nature of the fatty acid at the sn-2 position. The order of decreasing preference was C18:2 > C20:4 = C18:1 > C16:0. The hydrolyses of the molecular species were differentially affected by heating at 60 degrees C. An investigation into the effect of nucleotides on the activity of the enzyme showed that guanosine 5′-[gamma-thio]triphosphate (GTP[S]) inhibited the hydrolysis of PC by phospholipase A1 activity, whereas GTP, guanosine 5′-[beta-thio]diphosphate (GDP[S]), GDP, ATP and adenosine 5′-[gamma-thio]triphosphate (ATP[S]) did not affect the activity. The inhibitory effect of GTP[S] on phospholipase A1 activity was blocked by preincubation with GDP[S]. A differential effect of GTP[S] on the hydrolysis of different molecular species was also observed. Taken together, the results of this study suggest the presence of more than one phospholipase A1 in the microsomes with different substrate specificities, which act sequentially with lysophospholipase A2 to release linoleic or arachidonic acid selectively from PC under resting conditions. Upon stimulation and activation of the G-protein, the release of fatty acids would be inhibited.

scholarly journals Propagation of Action Potentials and the Structure of the Nexus in Cardiac Muscle

1965 ◽  
Vol 48 (5) ◽  
pp. 797-823 ◽  
Author(s):  
L. Barr ◽  
M. M. Dewey ◽  
W. Berger
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Action Potentials ◽  
Structural Changes ◽  
Sucrose Solution ◽  
Electrical Coupling ◽  
Intercalated Discs ◽  
Sucrose Gap ◽  
Specialized Structure ◽  
Frog Atrium

The hypothesis that the nexus is a specialized structure allowing current flow between cell interiors is corroborated by concomitant structural changes of the nexus and changes of electrical coupling between cells due to soaking in solutions of abnormal tonicity. Fusiform frog atrial fibers are interconnected by nexuses. The nexuses, desmosomes, and regions of myofibrillar attachment of this muscle are not associated in a manner similar to intercalated discs of guinea pig cardiac muscle. Indeed, nexuses occur wherever cell membranes are closely apposed. Action potentials of frog atrial bundles detected extracellularly across a sucrose gap change from monophasic to diphasic when the gap is shunted by a resistor. This indicates that action potentials are transmitted across the gap when sufficient excitatory current is allowed to flow across the gap. When the sucrose solution in the gap is made hypertonic, propagation past the gap is blocked and the resistance between the cells in the gap increases. Electron micrographs demonstrate that the nexuses of frog atrium and guinea pig ventricle are ruptured by hypertonic solutions.

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