Modulation of purinergic neurotransmission

During the past 25 years ATP has become accepted as an important neurotransmitter at a wide variety of neuroeffector junctions, usually acting as a cotransmitter with NA, ACh, nitric oxide or a neuropeptide such as NPY or VIP. The details of the storage and release of ATP with its cotransmitters has yet to be resolved. However, recent studies indicate that there is more than one population of storage vesicles in the nerves, since the release of the various cotransmitters varies over time and can be differentially modulated by drugs. The subclassification of P2 receptors has advanced dramatically in the past few years due to the use of molecular biology methods allowing the cloning and expression of 14 different subclasses of P2 receptors, seven P2X and seven P2Y. Determination of the functional significance of the various receptor subtypes would be helped by the development of selective agonists and antagonists. The neurotransmitter action of ATP at visceral and vascular smooth muscle P2X receptors has been elucidated in considerable detail. ATP induces a transient inward current via ligand-gated channels, which produces EJPs, action potentials and a phasic contraction of the effector tissue. ATP's neurotransmitter actions appear to be curtailed by the action of ATPases. It has been assumed that this ATPase activity is due to membrane bound ecto-ATPases on the surface of the effector tissue, however, the recently identified soluble ATPase released during nerve stimulation could also be involved in inactivation of ATP. The relative importance of ecto-ATPase and the releasable ATPase is yet to be determined.