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 Ca(2+) -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 Ca(2+)-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.
Zhang
L
L
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Rodríguez Del Castillo
A
A
Trifaró
J M
JM
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D005089:Exocytosis; D018260:Gelsolin; D006632:Histamine / Q000494:pharmacology*; D007700:Kinetics; D008840:Microfilament Proteins / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D018260:Gelsolin; D008840:Microfilament Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D013729:Terpenes; C065395:scinderin; D019284:Thapsigargin; D006632:Histamine; D010738:Type C Phospholipases; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine