Purinergic nerves and receptors

The presence of a non-cholinergic, non-adrenergic component in the vertebrate autonomic nervous system is now well established. Evidence that ATP is the transmitter released from some of these nerves (called "purinergic') includes: (a) synthesis and storage of ATP in nerves: (b) release of ATP from the nerves when they are stimulated; (c) exogenously applied ATP mimicking the action of nerve-released transmitter; (d) the presence of ectoenzymes which inactivate ATP; (e) drugs which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. A basis for distinguishing two types of purinergic receptors has been proposed according to four criteria: relative potencies of agonists, competitive antagonists, changes in levels of cAMP and induction of prostaglandin synthesis. Thus P1 purinoceptors are most sensitive to adenosine, are competitively blocked by methylxanthines and their occupation leads to changes in cAMP accumulation; while P2 purinoceptors are most sensitive to ATP, are blocked (although not competitively) by quinidine, 2-substituted imidazolines, 2,2'-pyridylisatogen and apamin, and their occupation leads to production of prostaglandin. P2 purinoceptors mediate responses of smooth muscle to ATP released from purinergic nerves, while P1 purinoceptors mediate the presynaptic actions of adenosine on adrenergic, cholinergic and purinergic nerve terminals.