DEXTRO AND LEVOROTATORY ISOMERS OF N-PHENYLISOPROPYLADENOSINE - STEREOSPECIFIC EFFECTS ON CYCLIC AMP-FORMATION AND EVOKED SYNAPTIC RESPONSES IN BRAIN-SLICES

The stereoisomers of N6-phenylisopropyladenosine elicit accumulations of cyclic AMP in brain slices via interaction with adenosine-receptors. The response in guinea pig cerebral cortical slices and in rat hippocampal slices is blocked by theophylline and potentiated by biogenic amines. A chelator, EGTA, potentiates the response to phenylisopropyladenosine in guinea pig cerebral cortical slices. The 1-isomer (EC50 25 μM) is four- to five-fold more potent than the d-isomer in eliciting accumulations of cyclic AMP in brain slices. In a rat coronal hippocampal slice in vitro, 1-phenylisopropyladenosine (IC50 ∼ 0.7 μM) reduces the amplitude of evoked synaptic responses generated via a monosynaptic pathway to the CA1 pyramidal neurons. The d-isomer is nearly one hundred-fold less potent. Thus, the adenosine-receptors involved in the electrophysical response appear much more stereoselective for the 1-isomer of phenylisopropyladenosine than the adenosine-receptors involved in cyclic AMP-generation in brain slices. © 1979.