| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
1)Negative surface charges activating Ca^<2+>-mobilizing receptors
The negative charges on the membrane surface may modify various types of functional protein including membrane receptors or G-protein/effector complex. The charges are neutralize or screened by positively charged ions in the solution, so I have introduced divalent or trivalent cations to neutralize the surface charges and studied effect of them. Excess divalent (Ca, Mg, Ba, Sr, Mn), trivalent(La), or polyvalent organic cation(protamine) all induced heparin-sensitive rise in [Ca^<2+>]i, suggesting that the charge neutralization produces inositol trisphosphate thereby increasing [Ca^<2+>]i, presumably through activation of surface receptors and/or receptor complex.
2)Control of inositol polyphosphate receptors by arachidonate
Effect of inositol polyphosphates (InsP3 or InsP4) introduced into single pancreatic acinar cells were studied by monitoring a rise in [Ca^<2+>]i with Ca^<2+>-dependent ionic currents. In the presence of phospholipase inhibitor, 4-BPB, the Ca^<2+> response was markedly enhanced. In contrast, the response was abolished by the presence of exogenous arachidonate. The results suggest that formation of arachidonate after increases in [Ca^<2+>]i can inhibit further rises in [Ca^<2+>]i.
3)Localized rise in [Ca^<2+>]i directly triggering exocytotic granular fusion
Pancreatic acinar cells shows a localized luminal increase in [Ca^<2+>]i after stimulation of either ACh or InsP3. Increases in membrane capacitance were studied in ACh stimulation and they were temporally correlated with the localized rise in [Ca^<2+>]i. Therefore we conclude that such rise in [Ca^<2+>]i is enough to trigger the exocytotic enzyme secretion in polarized exocrine cells.
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