scholarly journals Phosphodiesterases Inhibition Enhances the Effect of Glucagon on Cardiac Automaticity in the Isolated Right Ventricle of the Rat

2011 ◽  
pp. 189-192
Author(s):  
C. GONZALEZ-MUÑOZ ◽  
J. HERNÁNDEZ
Keyword(s):  
Right Ventricle ◽  
Cyclic Nucleotide ◽  
Rat Myocardium ◽  
Response Curves ◽  
Cyclic Nucleotide Phosphodiesterases ◽  
Effect Concentration ◽  
Ventricular Automaticity ◽  
A Minor ◽  
Cardiac Automaticity

We evaluated the effect of glucagon on cardiac automaticity as well as the possible role of cyclic nucleotide phosphodiesterases (PDE) in regulating this effect. Concentration response curves for glucagon in the absence and in the presence of the non-selective PDE inhibitor IBMX were performed in the isolated right ventricle of the rat. We found that glucagon produces only a minor increase of ventricular automaticity (11.0±4.1, n=5) when compared to the full agonist of β-adrenoceptor isoproterenol (182.2±25.3, n=7). However, IBMX enhances the maximal efficacy of glucagon on cardiac automaticity (11.0±4.1, in the absence and 45.3±3.2 in the presence of IBMX, n=5, P<0.05). These results indicate that PDE blunts proarrhythmic effects of glucagon in rat myocardium.

scholarly journals Simulations of the roles of multiple cyclic nucleotide phosphodiesterases

1982 ◽  
Vol 202 (1) ◽  
pp. 125-132 ◽  
Author(s):  
C H Reynolds
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Nucleotide ◽  
Maximum Velocity ◽  
Maximal Activity ◽  
Hormone Concentration ◽  
Response Curves ◽  
Cyclic Nucleotide Phosphodiesterases ◽  
Michaelis Constants ◽  
Nucleotide Phosphodiesterases

1. Simulations were performed using a model for cellular cyclic AMP metabolism involving a hormone-activated adenylate cyclase and two cyclic nucleotide phosphodiesterases with different Michaelis constants. 2. The response curves of cyclic AMP concentration as a function of hormone concentration were affected by regulating the phosphodiesterases. The maximum velocity of the high-affinity phosphodiesterase (V1) was important in determining the position of the response curve; when v1 was less than the maximal activity of adenylate cyclase (Vc), sigmoid response curves were readily produced. The maximum attainable concentration of cyclic AMP was determined primarily by V1 when Vc less than V1, and primarily by the activity of the low-affinity enzyme when Vc greater than V1 (V2 much greater than Vc in all cases). 3. The glucagon-stimulated adenylate cyclase and insulin-stimulated phosphodiesterase of the rat liver plasma membrane were simulated using experimentally determined values for the enzyme-kinetic parameters, and a considerable potential for regulation of the system by insulin was demonstrated. 4. Other possible functions for the regulation of phosphodiesterases are considered, in particular the value of increasing the speed of response to decreases in hormone concentration.

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