| Research Abstract |
Pharmacological studies on the mechanism of ATP-release :
In the the rat caudal arteries, noradrenaline (NA) evoked a significant release of ATP and its metabolites, which was abolished by prazosin, Ca^<2+> free and rubbing of endothelium. The release of ATP was increased by the sodium-potassium exchange solution. But, 40 mM KC1 solution and hypertonic solution reduced the release of ATP.Therefore, depolarization may facilitate the release of ATP.It is reported that the function of gap junction is prevented by hyperosmolarity. L-heptanol, gap junction inhibitor, abolished the release of ATP.
These suggest that the mechanisms of ATP-release is closely associated with Ca^<2+> influx and gap junction in voltage depent manner.
Microscopic studies on the mechanism of ATP-release :
In the rat caudal arteries, NA clearly raised intracellular Ca^<2+> levels in the endothelial and smooth muscle cells. On the other hand, in the cultured endothelial cells isolated from the rat caudal artery, NA did n
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ot raise intracellular Ca^<2+> level. Also, NA did not evoke the release of ATP in the cultured cells.
These suggest that NA-evoked ATP-release is closely associated with Ca^<2+> mobilization in both endothelial and smooth muscle cells.
Studies on the mechanisms of ATP and Nitric oxide :
In the rat caudal arteries, bradykinin (BK) produced endothelium-dependent and L-NAME-sensitive relaxation, but did not evoke the release of ATP.BK clearly raised intracellular Ca^<2+> levels in the endothelial and smooth muscle cells of the caudal artery. Also, in the cultured cells, BK clearly raised intracellular Ca^<2+> levels, but did not evoke the release of ATP.
These results suggest BK-evoked NO-release is closely associated with Ca^<2+> mobilization in endothelial cells alone and BK receptor does not couple with the mechanisms of ATP-release.
From the present results, there may be no linkage between the mechanisms of ATP-release coupled with alpha_1-adrenoceptor and NO-release coupled with BK-receptor, although both releases are closely associated with Ca^<2+>. As one possibility, it is suggested that intracellular Ca^<2+> mobilization in smooth muscle cells may be involved in the release of ATP from endothelial cells and gap junctionbetween smooth muscle, and endothelial cells may play an important roles. Less
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