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
L. Zhang et al., 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, Journal of neurochemistry, 65(3), 1995, pp. 1297-1308
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.