The overall objective of this research,is to further our knowledge of the mechanisms of transmitter release and its modulation by adenosine derivatives. For this next period of support,it is intended to use electrophysiological,luminometric and liposome-based methods to study the following four aspects of purinergic transmission in the vertebrate peripheral nervous system:1) We will study further how adenosine receptor activation is transduced into the inhibition of acetylcholine (ACh) secretion at motor nerve endings. Does adenosine inhibit ACh release by reducing Ca entry through voltage-gated membrane channels or impair the intracellular actions of Ca? 2) We will study the effects of adenosine in stimulating quantal transmitter release. Both the receptors responsible for increasing transmitter release and the mechanisms underlying the stimulatory effect of adenosine will be studied at mammalian motor nerve terminals and at nerve endings in submucous plexus of the mammalian enteric nervous system. 3) We will investigate the possibility that ATP may be an excitatory neurotransmitter in the submucous plexus. Both the postsynaptic effects of ATP derivatives and the calcium-dependent release of ATP will be studied. 4) We will investigate the possibility that adenosine is a modulator of peripheral synaptic plasticity reflected as long-term potentiation in frog sympathetic chain ganglia. Adenosine and its congeners,by their actions on synaptic junctions,have been implicated as natural mediators of a number of physiological, behavioral and pathological processes. Studying the mechanisms by which adenosine exerts its physiological effects at sites in the vertebrate nervous system that allow accurate electrophysiological measurements of secretions is likely to provide useful basic information on the underlying mechanisms by which purines regulate neuronal behavior.
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