PMID- 8596048
OWN - NLM
STAT- MEDLINE
DCOM- 19960415
LR  - 20181130
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 156
IP  - 5
DP  - 1996 Mar 1
TI  - The phosphatidylinositol 3-kinase inhibitor wortmannin blocks mast cell 
      exocytosis but not IL-6 production.
PG  - 1942-5
AB  - Phosphatidylinositol 3-kinase (PI3-kinase) activity has been shown to be 
      important in cellular signaling via receptors associated with tyrosine kinases 
      and receptors coupled to small or heterotrimeric G proteins. The importance of 
      this activity in mast cell degranulation, leukotriene C4 generation, and IL-6 
      production was examined in mouse bone marrow-derived mast cells stimulated by 
      high affinity IgE receptor cross-linking, direct influx of calcium, and/or 
      adenosine receptor agonist exposure. Wortmannin, a fungal metabolite that at 
      nanomolar concentrations inhibits PI3-kinase relatively specifically, blocked the 
      release of granule-associated mast cell mediators independent of the secretory 
      stimulus used. This inhibition was most prominent after a 2- to 5-min 
      preincubation with wortmannin and was equally effective in cells additionally 
      treated with exogenous N-ethylcarboxamidoadenosine to potentiate preformed 
      mediator release. Mast cell production of leukotriene C4 20 min after activation 
      or IL-6 16 h after activation was unaffected by up to 100 nM of wortmannin 
      exposure. Mast cells preincubated with wortmannin failed to develop the classic 
      electronmicroscopic evidence of granule swelling and fusion, increased membrane 
      ruffling, or exocytosis upon Ag challenge. Activation of PI3-kinase appears to be 
      critical for mast cell degranulation but is not required for arachidonic acid 
      metabolism or cytokine production to occur. Furthermore, the inhibition of mast 
      cell secretion by wortmannin is not stimulus specific but is evident for both IgE 
      receptor cross-linking and direct calcium influx.
FAU - Marquardt, D L
AU  - Marquardt DL
AD  - Department of Medicine, University of California, San Diego, La Jolla 92093, USA.
FAU - Alongi, J L
AU  - Alongi JL
FAU - Walker, L L
AU  - Walker LL
LA  - eng
GR  - AI-00961/AI/NIAID NIH HHS/United States
GR  - AI-25507/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Androstadienes)
RN  - 0 (Interleukin-6)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/*pharmacology
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Bone Marrow Cells
MH  - Cell Degranulation/drug effects
MH  - Exocytosis/*drug effects
MH  - Interleukin-6/*biosynthesis
MH  - Mast Cells/drug effects/*enzymology/ultrastructure
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphotransferases (Alcohol Group Acceptor)/*antagonists & inhibitors
MH  - Wortmannin
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1996 Mar 1;156(5):1942-5.