A possible role as a neuromodulator of extraneuronally released-ATP.

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The research project on the above title to 1991 from 1990 was attempted to elucidate further characteristics and physiological roles of extraneurofial ATP release from smooth and cardiac muscles of guinea-pig. Amounts of ATP and ACh in sample media were measured -by a luciferi. n-luciferase assay and HPLC-ECD system, respectively. This report is mainly composed of the following three contents. 1. ATP release from smooth muscles : ATP releases from the vas deferens and ileum were effectively caused by NA and ACh, respectively, compared to other receptor agonists such as substance P. - The evo-ked-ATP release was markedly prohibited by respective receptor antagonists, i. e., prazosin and atropine. alpha, beta-Methylene ATP (alpha, beta-mATP), a P_2-agonist, also produced a suramin (P_2-antagonist) sensitive ATP release from these tissues, indicating the existence of ATP evoked-ATP release system. There seems to be a coupling mechanism between transmitters' receptor stimulation and postju … More nctional ATP release in smooth muscles. 2. ATP release from cardiac muscles : Cardiotonics, e. g., isoproterenol, (Iso), markedly enhanced the contraction and the subsequent ATP release. The enhancement by Iso of ATP release was antagonized by propranolol, but not by butoxamine, a beta_2-antagonist, thus, showing that the origin of the release seems to be, primarily, postjunctional sites. 3. Roles of extraneuronally released-ATP : Electrically evoked-ACh release from the ileal preparation was reduced by alpha, beta-mATP as well as adenosine. As stated above, since alpha, beta-mATP per se elicited the ATP release, the released ATP is enzymatically changed to adenosine and the nucleoside may modulate the neurotransmission. ATP produced a contraction coupled with activation of Ca^<2+>-influx in smooth muscles. Both the responses were completely blocked by nifedipine, a Ca^<2+>-antagonist, implying an activation by ATP of voltage gated-Ca^<2+>-channels. In conclusion, there is an extraneuronal ATP release which is elicited by activating transmitters' receptors in smooth and cardiac muscles and the released ATP may serve as a neuromodulator or a neurostimulator in autonomic neurotransmission. Less