Antagonism of presynaptic adenosine receptors by theophylline 9-beta-D-riboside and 8-phenyltheophylline.

Theophylline 9-beta-D-riboside and 8-phenyltheophylline were evaluated as presynaptic adenosine receptor antagonists in the rat vas deferens in vitro. Stimulation of presynaptic adenosine receptors, which results in an inhibition of the twitch response to electrical field stimulation, was achieved with 2-chloroadenosine, an adenosine analogue that appears not to be a substrate for the adenosine transport system. The presynaptic inhibitory action of 2-chloroadenosine was antagonized by theophylline (10 and 100 microM) and by 8-phenyltheophylline (10 microM) but not by theophylline 9-beta-D-riboside (100 microM). It is concluded that the addition of a ribose moiety to theophylline does not enhance the antagonist potency of the molecule but actually renders the compound inactive. However, 8-phenyltheophylline is approximately three times more potent than theophylline at presynaptic adenosine receptors.