Novel characteristics of ATP as a potential neuro-co-transmitter.

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Recent findings provide evidence that ATP is capable of acting as a neuro-co-transmitter along with the classical transmitter,noradrenaline(NA)in adrenergically dominant tissues.The research project from 1986 to 1987 was designed to clarify further characteristics of cotransmission of NA and ATP from guinea-pig vas deferens.The study with HPLC-ECD in the first year disignated that ouabain(100<micrn>and/or monesin(10<micrn>),but not high KCI,produced a prominent liberation of granular NA which was mediated by intracellular Ca^<2+> originating, presumably,from mitochondrial store sites.In addition to measuring this NA release.the investigation in 1987 was to measure ATP released from the tissue by a lumicounting method in the presence of secretagogues such as ouabain plus monensin and high KCI.Ouabain plus monensin caused a moderate outflow of atp which was markedly diminished by both 6-hydroxydopamine and prazosin,thus,meaning primarily an extraneuronal release of the nucleotide.On the other hand,an outstanding liberation of ATP by high KCI was highly decreased by 6-hydroxydopamine or Ca^<2+>-removal,but not by prazosin,indicating,mainly a neuronal ATP release.Amounts of neuronal release of ATP by ouabain plus monensin and by high KCl were 1.7<micrn>g and 11.2<micrn>g/g wet weight,respectively.On the other hand,that of neuronal release of NA by the same procedures amounted to 7.7<micrn>g and 1.7<micrn>g/g wet weight,respectively.These results strongly support a possibility that NA and ATP are co-released from two different store sites of the adrenergic nerves by depolarization and elevation of intracellular Na^+ levels.