Adenosine inhibits the positive inotropic effect of 3‐isobutyl‐1‐methylxanthine in papillary muscles without effect on cyclic AMP or cyclic GMP
1988
1
Adenosine and the adenosine receptor agonist (—)-N6-phenylisopropyladenosine (PIA) produced a small positive and negative inotropic effect, respectively, in isolated electrically driven papillary muscles of guinea-pigs.
2
Adenosine (100 μmol 1−1) had no effect on cyclic AMP or cyclic GMP content. PIA (100 μmol 1−1) slightly increased cyclic AMP.
3
In the presence of 3-isobutyl-1-methylxanthine (IBMX; 60 μmol 1−1), which increased force of contraction 2 fold, adenosine and PIA exerted strong negative inotropic effects. PIA was more potent than adenosine (mean IC25 2.1 and 168 μmol 1−1, respectively).
4
In contrast, the nucleosides did not affect the increase in force of contraction produced by elevating extracellular Ca2+ concentration.
5
The IBMX-antagonistic effects of adenosine and PIA were not accompanied by modification of the IBMX-induced increase in cyclic AMP and cyclic GMP.
6
The effects of adenosine and PIA on force of contraction were accompanied by a partial reversal of the IBMX-induced increase in the maximal rate of depolarization of slow action potentials.
7
It is concluded that adenosine and PIA are able to attenuate the positive inotropic effect of a phosphodiesterase inhibitor. This effect is unlikely to be due to a reduction of the IBMX-induced increase in cyclic AMP content. It is conceivably due to an inhibition of the stimulant action of cyclic AMP on slow Ca2+ channels leading to the reduction of the slow inward current which in turn reduces force of contraction.
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