ADENOSINE DERIVATIVES AND CHOLINERGIC NERVE ENDINGS

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The aim of this project is to study further the involvement of adenosine derivatives in the function of cholinergic nerve endings in the peripheral nervous system. With respect to the release of adenine nucleotide, is there an association between all forms of acetylcholine (ACh) secretion and the release of adenosine triphosphate (ATP). Specifically, ACh release will be evoked by various methods and the release of ATP and ACh assayed. Bioassay chemical methods will be used to detect ACh release and the firefly bioluminescence reaction employed to detect ATP release. With respect to the effects of adenosine derivatives, an electrophysiological study of ACh release will be made to characterize the specific adenosine receptors that mediate inhibition and enhancement of ACh release at motor nerve endings and the putative adenosine phosphate receptors that inhibit ACh release at preganglionic nerve endings. The potency sequences for various agonists and antagonists and the relationship between adenosine or purinergic receptor activation and intracellular modulators such as Ca and cyclic necleotides will be investigated. Liposomes will be employed as a means of delivering Ca or purine derivatives to the cytoplasm of the nerve ending. As abnormal adenine necleotide metabolism occurs in certain forms of muscle disease (e.g. Duchenne dystrophy), and ACh release is impaired at ganglia in familial dysautonomia, studying the normal relationship between adenosine derivatives and neuromuscular function should provide a valuable framework for future studies on the diseased cholinergic synapses.