PMID- 1674588
OWN - NLM
STAT- MEDLINE
DCOM- 19910621
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 39
IP  - 5
DP  - 1991 May
TI  - 12-hydroperoxyeicosatetraenoic acid inhibits main platelet functions by 
      activation of soluble guanylate cyclase.
PG  - 671-8
AB  - 12-Hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) as well as several 
      other fatty acid hydroperoxides are potent inhibitors of platelet activation. 
      12-HPETE but not 12-hydroxy-5,8,10,14-eicosatetraenoic acid blocks the U46619- 
      and the thrombin-triggered aggregation of aspirin-treated platelets, dose 
      dependently. 12-HPETE suppresses thromboxane production by inhibiting platelet 
      cyclooxygenase and stimulates its own production by increasing lipoxygenase 
      activity, although this effect does not explain the inhibitory activity of 
      12-HPETE during the initial phase of cell activation. The inhibitory effect is 
      related to altered calcium homeostasis during platelet activation. 12-HPETE 
      inhibits calcium release from intracellular stores and modifies the influx of 
      extracellular calcium. The inhibitory effect on calcium mobilization is explained 
      by activation of soluble guanylate cyclase. These inhibitory properties are 
      shared by sodium nitroprusside, a compound known to activate soluble guanylate 
      cyclase. Fatty acid hydroperoxides, especially 12-HPETE, produce a rapid and 
      dose-dependent activation of soluble guanylate cyclase, using intact human 
      platelets as a detection system. Activation of the enzyme shows a position isomer 
      specificity, with 12-HPETE being the most potent activator. The generation of the 
      labile lipoxygenase product 12-HPETE during platelet activation may modulate 
      platelet reactivity by increasing cyclic GMP. This pathway may contribute to a 
      physiological feedback mechanism to limit the size of a growing platelet plug.
FAU - Brune, B
AU  - Brune B
AD  - Faculty of Biology, University of Konstanz, Federal Republic of Germany.
FAU - Ullrich, V
AU  - Ullrich V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Eicosanoids)
RN  - 0 (Leukotrienes)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Vasoconstrictor Agents)
RN  - 67675-13-2 (12-HPETE)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Blood Platelets/*drug effects/enzymology
MH  - Calcium/blood
MH  - Cyclic GMP/blood
MH  - Eicosanoids/metabolism
MH  - Enzyme Activation/drug effects
MH  - Guanylate Cyclase/*drug effects
MH  - Humans
MH  - Leukotrienes/*pharmacology
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Vasoconstrictor Agents/pharmacology
EDAT- 1991/05/01 00:00
MHDA- 1991/05/01 00:01
CRDT- 1991/05/01 00:00
PHST- 1991/05/01 00:00 [pubmed]
PHST- 1991/05/01 00:01 [medline]
PHST- 1991/05/01 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1991 May;39(5):671-8.