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+-de pendent release of catecholamines. However, conflicting evidence exist s as to the source of Ca2+ utilized in histamine-evoked secretion. Her e we report that histamine-H-1 receptor activation induces redistribut ion of scinderin, a Ca2+-dependent F-actin severing protein, cortical F-actin disassembly, and catecholamine release. Histamine evoked simil ar patterns of distribution of scinderin and filamentous actin. The ra pid responses to histamine occurred in the absence of extracellular Ca 2+ and were triggered by release of Ca2+ from intracellular stores. Th e trigger for the release of Ca2+ was inositol 1,4,5-trisphosphate bec ause U-73122, a phospholipase C inhibitor, but not its inactive isomer (U-73343), inhibited the increases in IP3 and intracellular Ca2+ leve ls, scinderin redistribution, cortical F-actin disassembly, and catech olamine 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 ca techolamine secretion in response to histamine. Calphostin C and chele rythrine, two inhibitors of protein kinase C, blocked all responses to histamine with the exception of the release of Ca2+ from intracellula r stores, This suggests that protein kinase C is involved in histamine -induced responses. The results also show that in the absence of F-act in disassembly, rises in intracellular Ca2+ concentration are not by t hemselves capable of triggering catecholamine release.