PMID- 8764366
OWN - NLM
STAT- MEDLINE
DCOM- 19960923
LR  - 20061115
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 278
IP  - 1
DP  - 1996 Jul
TI  - U-73122: a potent inhibitor of human polymorphonuclear neutrophil adhesion on 
      biological surfaces and adhesion-related effector functions.
PG  - 320-9
AB  - We have reported that U-73122 (1-[6-[[17 
      beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole- 2,5-dione) an 
      inhibitor of phospholipase C-dependent processes in human polymorphonuclear 
      neutrophils (PMN) and platelets, potently suppresses the responsiveness of 
      suspended PMN and platelets to receptor agonists. We demonstrate here that 
      U-73122 caused a concentration-dependent (10-800 nM) inhibition of 
      N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor-alpha (TNF alpha), 
      interleukin-8 and phorbol myristate acetate (PMA)-triggered PMN adhesion on 
      fibronectin, fetal bovine serum or keyhole limpet hemocyanincoated microtiter 
      plates. U-73122 also inhibited PMN adherence to and transmigration through 
      TNF-alpha-activated endothelium (IC50 < 50 nM). Further, U-73122 suppressed 
      interleukin-8, N-formylmethionyl-leucyl-phenylalanine and PMA-stimulated 
      up-regulation of the beta 2-integrin, Mac-1 (CD11b/CD18), on the PMN surface 
      (IC50 < 1.3 microM). U-73122 also caused a time-(15-120 min) and 
      concentration-dependent inhibition (IC50 = 25-100 nM) of the 
      N-formyl-methionyl-leucyl-phenylalanine-, TNF alpha- and PMA-elicited 
      adhesion-dependent, oxidative burst, measured as hydrogen peroxide (H2O2) 
      production, in PMN. The CD18-dependent extracellular release of lactoferrin from 
      PMN activated with these stimuli was also suppressed by U-73122. U-73343 
      (1-[6-[[17 beta-3- 
      methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidine dione), a close 
      analog of U-73122, did not affect PMN responsiveness.
FAU - Smith, R J
AU  - Smith RJ
AD  - Cell Biology and Inflammation Research, Pharmacia & Upjohn, Inc., Kalamazoo, 
      Michigan, USA.
FAU - Justen, J M
AU  - Justen JM
FAU - McNab, A R
AU  - McNab AR
FAU - Rosenbloom, C L
AU  - Rosenbloom CL
FAU - Steele, A N
AU  - Steele AN
FAU - Detmers, P A
AU  - Detmers PA
FAU - Anderson, D C
AU  - Anderson DC
FAU - Manning, A M
AU  - Manning AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Estrenes)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrrolidinones)
RN  - 112648-68-7 
      (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Adhesion/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Estrenes/*pharmacology
MH  - Humans
MH  - Neutrophils/*drug effects
MH  - Phosphodiesterase Inhibitors/*pharmacology
MH  - Pyrrolidinones/*pharmacology
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1996 Jul;278(1):320-9.