Role of adenine compounds in autonomic neurotransmission.

Clearly adenine compounds exert numerous effects throughout the autonomic nervous system. The responses of various peripheral tissues to purines are summarized in Table 2. The evidence supporting a possible excitatory neurotransmitter function for ATP is very good in the vas deferens and good in both the bladder detrusor and certain blood vessels. ATP may also be an excitatory neurotransmitter in the colon, hepatocytes and frog atrium. These responses appear to be mediated by P2x-purinoceptors. There is good evidence supporting a role for ATP as an inhibitory neurotransmitter in the taenia coli and duodenum, and some support in the anal sphincter and possibly the rabbit portal vein; these responses appear to be mediated by P2y-purinoceptors. There is good evidence against ATP being an inhibitory neurotransmitter in the stomach fundic muscle and ileum. ATP (or more likely its metabolite adenosine) may act as an inhibitory neurotransmitter by interacting with postsynaptic P1-purinoceptors in cultured sympathetic neurones and also in the parasympathetic vesicle ganglion of the cat. It seems likely that ATP released from heart, platelets or vascular endothelium could be an endogenous relaxant of blood vessels through its actions on the endothelium. Although the addition of exogenous adenosine affects many tissues, evidence supporting modulatory functions for endogenous extracellular adenosine has only been clearly demonstrated in the ileum, gallbladder, vas deferens, fallopian tubes, kidney, blood vessels, carotid sinus, heart and adipose tissue. Both ATP and adenosine, released during periods of hypoxia or ischemia, could exert negative inotropic, chronotropic and dromotropic actions in the heart. In many cases, the potential sources of extracellular purines have not been established. This is particularly important when attempting to establish a neurotransmitter function for ATP in a tissue. For instance, the one outstanding piece of evidence required to confirm that ATP is an excitatory neurotransmitter released from sympathetic nerves in blood vessels is the unequivocal demonstration that it is, in fact, released from the sympathetic nerves when they are stimulated. To date, only the release of radiolabeled metabolites of ATP, possibly from post- rather than presynaptic sites, has been detected. Studies of the release of ATP are complicated by its rapid degradation extracellularly by ecto-ATPase. Unfortunately, there are no specific inhibitors of ecto-ATPase available at present, but one hopes that a suitable inhibitor will be developed shortly.(ABSTRACT TRUNCATED AT 400 WORDS)