Histamine‐Evoked Chromaffin Cell Scinderin Redistribution, F‐Actin Disassembly, and Secretion: In the Absence of Cortical F‐Actin Disassembly, an Increase in Intracellular Ca2+ Fails to Trigger Exocytosis

: Histamine is a known chromaffin cell secretagogue that induces Ca2+‐dependent release of catecholamines. However, conflicting evidence exists as to the source of Ca2+ utilized in histamine‐evoked secretion. Here we report that histamine‐H1 receptor activation induces redistribution of scinderin, a Ca2+‐dependent F‐actin severing protein, cortical 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 Ca2+ and were triggered by release of Ca2+ from intracellular stores. The trigger for the release of Ca2+ was inositol 1,4,5‐trisphosphate because U‐73122, a phospholipase C inhibitor, but not its inactive isomer (U‐73343), inhibited the increases in IP3 and intracellular Ca2+ levels, scinderin redistribution, cortical F‐actin disassembly, and catecholamine release in response to histamine. Thapsigargin, an agent known to mobilize intracellular Ca2+, blocked the rise in intracellular Ca2+ concentration, scinderin redistribution, F‐actin disassembly, and catecholamine secretion in response to histamine. Calphostin C and chelerythrine, two inhibitors of protein kinase C, blocked all responses to histamine with the exception of the release of Ca2+ from intracellular stores. This suggests that protein kinase C is involved in histamine‐induced responses. The results also show that in the absence of F‐actin disassembly, rises in intracellular Ca2+ concentration are not by themselves capable of triggering catecholamine release.