Influence of dipyridamol (Persantin) on myocardial adenosine metabolism

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Abstract

The degradation of adenine nucleotides to inosine in the ischemic myocardium of the dog is inhibited by about 80% by dipyridamol, which hinders the deamination of adenosine.

The Ki-values of dipyridamol for the intramyocardial deamination of adenosine in vivo are about 1000 times smaller (corresponding to a 1000 times stronger inhibition) than the inhibitory constants of dipyridamol for the enzymic deamination in vitro. The Ki-values of dipyridamol for the penetration of adenosine through the membranes of different blood cells and for the degradation of adenosine in the ischemic myocardium are of the same order of magnitude.

From the kinetic studies it appears that dipyridamol inhibits the degradation of adenosine within the myocardial cell by hindering its penetration through intracellular membranes prior to its enzymic deamination.

Dipyridamol also increases the resistance of the myocardial cell membrane to the penetration of adenosine out of the cell.

Thus it can be concluded that the diffusion of adenosine from the intracellular to the extracellular space cannot be essential for the coronary dilating action of dipyridamol and, therefore, not for the local metabolic regulation of coronary blood flow.

These findings suggest the existence of alternate or additional mechanisms to the postulated adenosine mechanism of local metabolic regulation of coronary blood flow.

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