Nicotinic stimulation of chromaffin cells causes disassembly of cortical F-actin networks and redistribution of scinderin, a Ca$\sp{2+}$-dependent F-actin severing protein. These Ca$\sp{2+}$-dependent events precede exocytosis. Activation of scinderin by Ca$\sp+$ may cause severing of F-actin and disassembly of actin networks leaving cortical areas of low cytoplasmic viscosity which are the sites of exocytosis. Histamine is a known chromaffin cell secretagogue which induces Ca$\sp+$-dependent release of catecholamines. However, conflicting evidence exists as to the source of Ca$\sp{2+}$ utilized in histamine-evoked secretion. Here we report that histamine-H$\sb1$ receptor activation induces scinderin redistribution, F-actin disassembly and catecholamine release. Histamine evoked similar patterns of distribution of scinderin and filamentous actin. The rapid responses to histamine occurred in the absence of extracellular Ca$\sp{2+}$ and were triggered by release of Ca$\sp{2+}$ from intracellular stores. The trigger for the release of Ca$\sp{2+}$ was inositol 1,4,5-triphosphate (IP$\sb3$) since U-73122, a phospholipase C inhibitor, but not its inactive isomer (U-73343), inhibited the increases in IP$\sb3$, intracellular Ca$\sp{2+}$, scinderin redistribution, cortical F-actin disassembly and catecholamine release in response to histamine. Thapsigargin, an agent known to mobilize intracellular Ca$\sp{2+}$, blocked the rise in intracellular Ca$\sp{2+}$, scinderin redistribution, F-actin disassembly and catecholamine secretion in response to histamine. However, thapsigargin did not modify the increase in IP$\sb3$ induced by histamine. Calphostin C and chelerythrine, two inhibitors of protein kinase C, blocked all responses to histamine with the exception of the release of Ca$\sp{2+}$ from intracellular stores. This suggests that protein kinase C is involved in histamine induced response. The results also show that without F-actin disassembly, raises in intracellular Ca$\sp{2+}$ are not by themselves capable of triggering catecholamine release.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/9991 |
| Date | January 1995 |
| Creators | Zhang, Li. |
| Contributors | Trifaro, J. M., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 132 p. |
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