Antagonism towards endogenous adenosine and inhibition of cGI-PDE in the cardiac effects of amrinone, milrinone and related analogues.
1. The effect of amrinone, milrinone and of three milrinone analogues was tested on spontaneous chronotropic and inotropic activity of guinea-pig isolated atria, on the activity of cGMP-inhibited phosphodiesterase (cGI-PDE) from guinea-pig heart and on specific binding of N6-cyclohexyl[3H]adenosine ([3H]CHA) to Ri adenosine receptors in guinea-pig atria. 2. The Ki-values towards [3H]CHA binding to Ri receptors were linearly related to the EC50S for the increase in force of contraction but not to the EC50S for the increase in frequency of the atria. The Ki values towards cGI-PDE were linearly related to the EC50S for the positive chronotropic effect.
Dorigo
P
P
Department of Pharmacology, University of Padova, Italy.
Gaion
R M
RM
Belluco
P
P
Borea
P A
PA
Guerra
L
L
Mosti
L
L
Floreani
M
M
Carpenedo
F
F
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology
D011728:Pyridones; C027513:N(6)-cyclohexyladenosine; D012110:Reserpine; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D020105:Milrinone; D000676:Amrinone; D000241:Adenosine