maticity induced by a local injury in the isolated right ventricle of the rat were studied. 2 In concentrations ranging from 0.1 to 100 nM, NECA significantly increased ventricular automaticity. This effect was more reproducible when the adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) was present at 5 nM, a concentration that blocks Al adenosine receptors.3 The excitatory effect of NECA was not observed when DPCPX was present at a concentration of 1O pM, which antagonizes both A1 and A2 adenosine receptors, as well as when rats were reserpinized. 4 In reserpinized rats, NECA increased ventricular automaticity in the presence of isoprenaline and the fl2-adrenoceptor antagonist, ICI-118,551, but not in the presence of the PI-adrenoceptor antagonists, bisoprolol or atenolol. 5 The A2a-selective adenosine receptor agonist, CGS-21680 (0.1 nM-10 Mm) was devoid of excitatory effect on ventricular automaticity. Binding studies of this compound to the rat ventricular membranes revealed that in the preparation there was no specific binding. 6 These results suggest that the excitatory effect of NECA on ectopic ventricular automaticity is dependent on endogenous catecholamines and is mediated by an A2 adenosine receptor which is in some way 'linked' to the P3-adrenoceptor. These A2 receptors do not appear to be of the A2a adenosine receptor subtype.

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The influence of phenobarbital pretreatment on liver concentration of digitoxin and its metabolites was studied in guinea-pigs after i.p. administration of the cardiac glycoside. During the first hour an increase in liver uptake was observed in pretreated animals. The differences detected in the hepatic subcellular distribution do not seem to explain the higher concentrations found in the liver of phenobarbital pretreated animals. About 80% of the liver radioactivity was found in the supernatants. Inhibition of digitoxin biotransformation by phenobarbital was demonstrated by chromatographic analysis of the organic soluble compounds present in the supernatants. The possible binding of digitoxin and its metabolites to soluble proteins of liver cytosol was excluded by thin-layer gel filtration. The decrease in digitoxin biotransformation seems to be the reason for the increase in liver uptake and for the decrease in bile concentrations, observed in phenobarbital pretreated animals.