Inhibitory action of adenosine and adenosine analogs on neurotransmission in the olfactory cortex slice of guinea pig - structure-activity relationships

Abstract

The postsynaptic potential (PSP) was recorded from thin slices of the olfactory cortex of the guinea pig. Application of adenosine and adenine nucleotides such as 5'-ATP, 5'-ADP and 5'-AMP in the incubation medium, depressed the amplitude of the PSP without altering the presynaptic fiber potential. The other purine and pyrimidine derivatives had no inhibitory effect. The inhibitory action of adenosine and adenine nucleotides on the PSP were manifest at concentrations of 5 microM-1 mM. Adenosine, 5'-ATP, 5'-ADP and 5'-AMP were equipotent in evoking depression of PSPs. Inhibition occurred within 10-20 sec after administration of the agents and the depressant effect disappeared rapidly after the removal of the compounds from the medium. Theophylline reversed and prevented the inhibition produced by adenosine and adenine nucleotides. To test the structure-activity relationships of these compounds, adenosine analogs and adenine nucleotide derivatives were applied to the medium. The 6-aminopurine riboside (adenosine radical) was found to be essential for inhibitory action on the PSP. Among adenosine analogs, the presence of at least one hydrogen atom in the amino group at the 6-position of the purine, and the OH group at the 2'-position of the ribose was essential for inhibitory activity.