|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1996 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1995 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Pharmacological Studies on the mechanism of ATP-release in the vascular endothelial cells.
In the endothelial cells of the rat caudal arteries, noradrenaline evoked a significant release of ATP and is metabolites, which was abolished in the absence of extracellular Ca^<2+>. The release of ATP was significantly enhanced by cyclopiazonic acid, Ca^<2+> pump inhibitor, and reduced by SK & F96365, receptor operated Ca^<2+> channel blocker. These suggest that the mechanism of ATP-release closely associated with Ca^<2+> influx through receptor operated Ca^<2+> channels.
It is well known that acetylcholine releases nitric oxide (NO) depending on Ca^<2+>. In the rat caudal arteries, acetylcholine produced an endothelium-dependent relaxation that was abolished in the presence of L-nitroarginine methylester, inhibitor of NO synthase. However, acetylcholine did not evoke the ATP-release. On the other hand, noradrenaline did not evoke the NO release, since L-nitroarginine methylester did not affect the concentration-contraction curve for noradrenaline at all. Therefore, there may be no linkage between the mechanisms of ATP-release coupled with alpha_1-adrenoceptor and NO release coupled with cholinoceptor, although both releases were closely associated with Ca^<2+>.
Microscopic studies on the mechanism of ATP-release in the vascular endothelial cells.
Ca^<2+> mobilization on the endothelial cells within the wall of rat caudal artery stimulated with noradrenaline and acetylcholine was studied, using confocal microscope and Indo-1-AM.Noradrenaline and acetylcholine clearly raised Ca^<2+> levels in endothelial cells. But, the number of cells responded to former was smaller than that of latter. Furthermore, the cells responded to noradrenaline did not respond to acetylcholine. These suggest a possibility that the Ca^<2+> mobilizations coupled with alpha_1-adrenoceptor may be different from that coupled with cholinoceptor.