Physiological importance of ATP released from nerve terminals and its degradation to adenosine in humans.

T he paper by Taddei et all in this issue of Circulation deals with two important physiological aspects of endogenous purine compounds, both of which have been controversial for quite some time. The first is the release of ATP from nerve terminals and the second, the antiadrenergic action of adenosine. In their study in humans, Taddei et al found evidence suggesting a) reflex vasoconstriction mediated in part by ATP and b) the modulation of this reflex by adenosine, a product of enzymatic degradation of ATP. The latter could be a manifestation of the antiadrenergic action of endogenous adenosine under experimental conditions that closely resemble physiological ones.' Thus, these observations demonstrate for the first time in humans that the release of ATP, its degradation to adenosine, and the inhibition of neurotransmitter release by adenosine constitute an important physiological regulatory feedback loop. The idea that some nerves release more than one transmitter was originally proposed by Burnstock2 in what has been termed the cotransmitter hypothesis.