Is adenosine the mediator of opiate action on neuronal firing rate?

Abstract

Despite recent advances^1,2, relatively little is known of the mechanism of action of opiate analgesics at the cellular level. There is evidence, however, that the inhibition of neurotransmitter release produced by morphine may be mediated by the initial release of adenosine^3–5; the effect is mimicked by adenosine and the actions of both adenosine and morphine are blocked by theophylline and enhanced by dipyridamole^3–5. When applied microiontophoretically, adenosine has also been shown to be a potent depressant of the firing rate of single neurones in the mammalian brain, and a similar depressant effect of morphine has been claimed to be stereospecific, antagonised by naloxone^6–9 and greatly reduced in animals made tolerant to, and dependent on, morphine^8,9. The experiments described here examine the effect of aminophylline, a soluble theophylline derivative, on these depressant effects. We have found that aminophylline will block responses to both morphine and adenosine, suggesting that the depressant responses to morphine may also be mediated by the local release of adenosine.