[38] Metabolism and function of phosphatidylinositol-derived arachidonic acid

1990 ◽  
pp. 676-691
Author(s):  
Lowell E. Hokin
Keyword(s):  
Arachidonic Acid ◽  
And Function

Platelet Suruival and Function in Rats with Enhanced Thrombotic Tendency

1985 ◽  
Vol 54 (04) ◽  
pp. 739-743 ◽  
Author(s):  
Federica Delaini ◽  
Elisabetta Dejana ◽  
Ine Reyers ◽  
Elisa Vicenzi ◽  
Germana De Bellis Vitti ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Nephrotic Syndrome ◽  
Platelet Function ◽  
Laboratory Tests ◽  
Thrombus Formation ◽  
The Other ◽  
Mean Survival Time ◽  
The Mean ◽  
And Function ◽  
Thrombotic Tendency

SummaryWe have investigated the relevance of some laboratory tests of platelet function in predicting conditions of thrombotic tendency. For this purpose, we studied platelet survival, platelet aggregation in response to different stimuli, TxB2 and 6-keto-PGFlα production in serum of rats bearing a nephrotic syndrome induced by adriamycin. These animals show a heavy predisposition to the development of both arterial and venous thrombosis. The mean survival time was normal in nephrotic rats in comparison to controls. As to aggregation tests, a lower aggregating response was found in ADR-treated rats using ADP or collagen as stimulating agents. With arachidonic acid (AA) we observed similar aggregating responses at lower A A concentrations, whereas at higher AA concentrations a significantly lower response was found in nephrotic rats, despite their higher TxB2 production. Also TxB2 and 6-keto-PGFlα levels in serum of nephrotic rats were significantly higher than in controls. No consistent differences were found in PGI2-activity generated by vessels of control or nephrotic rats.These data show that platelet function may appear normal or even impaired in rats with a markedly increased thrombotic tendency. On the other hand, the significance of high TxB2 levels in connection with mechanisms leading to thrombus formation remains a controversial issue.

Docosahexaenoic and Arachidonic Acid Influence on Preterm Baboon Retinal Composition and Function

2003 ◽  
Vol 44 (10) ◽  
pp. 4559 ◽  
Author(s):  
Guan-Yeu Diau ◽  
Ellis R. Loew ◽  
Vasuki Wijendran ◽  
Eszter Sarkadi-Nagy ◽  
Peter W. Nathanielsz ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
And Function

scholarly journals Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD

2001 ◽  
Vol 281 (4) ◽  
pp. H1697-H1703 ◽  
Author(s):  
Sean P. Didion ◽  
Christopher A. Hathaway ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
Blood Vessels ◽  
Basilar Artery ◽  
Normal Activity ◽  
Cerebral Blood Vessels ◽  
Cranial Window ◽  
Copper Zinc ◽  
Cerebral Arterioles ◽  
And Function

The goal of this study was to examine the role of endogenous copper/zinc (CuZn)-superoxide dismutase (SOD) on superoxide levels and on responses of cerebral blood vessels to stimuli that are mediated by nitric oxide (acetylcholine) and cyclooxygenase-dependent mechanisms (bradykinin and arachidonic acid). Levels of superoxide in the rabbit basilar artery were measured using lucigenin-enhanced chemiluminescence (5 μM lucigenin). Diethyldithiocarbamate (DDC; 10 mM), an inhibitor of CuZn-SOD, increased superoxide levels by ∼2.4-fold ( P < 0.05) from a baseline value of 1.0 ± 0.2 relative light units · min−1 · mm−2(means ± SE). The diameter of cerebral arterioles (baseline diameter, 99 ± 3 μm) was also measured using a closed cranial window in anesthetized rabbits. Topical application of DDC attenuated responses to acetylcholine, bradykinin, and arachidonate, but not nitroprusside. For example, 10 μM arachidonic acid dilated cerebral arterioles by 40 ± 5 and 2 ± 2 μm under control conditions and after DDC, respectively ( P < 0.05). These inhibitory effects of DDC were reversed by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (10 mM). Arachidonate increased superoxide levels in the basilar artery moderately under normal conditions and this increase was greatly augmented in the presence of DDC. These findings suggest that endogenous CuZn-SOD limits superoxide levels under basal conditions and has a marked influence on increases in superoxide in vessels exposed to arachidonic acid. The results also suggest that nitric oxide- and cyclooxygenase-mediated responses in the cerebral microcirculation are dependent on normal activity of CuZn-SOD.

REGULATION AND INHIBITION OF ARACHIDONIC ACID ω-HYDROXYLASES AND 20-HETE FORMATION

2005 ◽  
Vol 45 (1) ◽  
pp. 413-438 ◽  
Author(s):  
Deanna L. Kroetz ◽  
Fengyun Xu
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Enzyme Inhibitors ◽  
Biological Effects ◽  
Biological Significance ◽  
Substrate Selectivity ◽  
Altered Expression ◽  
Important Pathway ◽  
And Function ◽  
Cytochrome P450 4A

Cytochrome P450–catalyzed metabolism of arachidonic acid is an important pathway for the formation of paracrine and autocrine mediators of numerous biological effects. The ω-hydroxylation of arachidonic acid generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in numerous tissues, particularly the vasculature and kidney tubules. Members of the cytochrome P450 4A and 4F families are the major ω-hydroxylases, and the substrate selectivity and regulation of these enzymes has been the subject of numerous studies. Altered expression and function of arachidonic acid ω-hydroxylases in models of hypertension, diabetes, inflammation, and pregnancy suggest that 20-HETE may be involved in the pathogenesis of these diseases. Our understanding of the biological significance of 20-HETE has been greatly aided by the development and characterization of selective and potent inhibitors of the arachidonic acid ω-hydroxylases. This review discusses the substrate selectivity and expression of arachidonic acid ω-hydroxylases, regulation of these enzymes during disease, and the application of enzyme inhibitors to study 20-HETE function.

Disorders of platelet number and function

2010 ◽  
pp. 4506-4518
Author(s):  
Kathryn E. Webert ◽  
John G. Kelton
Keyword(s):  
Bone Marrow ◽  
Arachidonic Acid ◽  
Blood Vessel ◽  
Critical Role ◽  
Adenosine Diphosphate ◽  
Reticuloendothelial System ◽  
Glycoprotein Ib ◽  
Platelet Number ◽  
Key Features ◽  
And Function

Platelets are released from megakaryocytes in the bone marrow and circulate for 5 to 10 days before being cleared by the cells of the reticuloendothelial system. They play a critical role in haemostasis, with key features being (1) adhesion—when the wall of a blood vessel is damaged, platelets adhere to exposed collagen and other components of the subendothelium via the glycoprotein Ib receptor and other adhesive receptors; followed by (2) activation—release of thrombin, adenosine diphosphate, and arachidonic acid, which is converted by a cascade of enzymes into platelet activating agents including thromboxane A...

scholarly journals Loss of adipocyte phospholipase gene PLAAT3 causes lipodystrophy and insulin resistance due to inactivated arachidonic acid-mediated PPAR𝛾 signaling

2021 ◽  
Author(s):  
Nika Schuermans ◽  
Salima El Chehadeh ◽  
Dimitri Hemelsoet ◽  
Elke Bogaert ◽  
Elke Debackere ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Arachidonic Acid ◽  
Drug Target ◽  
Loss Of Function ◽  
Membrane Phospholipids ◽  
Partial Lipodystrophy ◽  
Severe Insulin Resistance ◽  
Diet Induced Obesity ◽  
Candidate Drug ◽  
And Function

PLAAT3 is a phospholipid modifying enzyme predominantly expressed in white adipose tissue (WAT). It is a candidate drug target as Plaat3 deficiency in mice protects against picornavirus infection and diet-induced obesity. We identified four patients with homozygous loss-of-function mutations in PLAAT3, presenting with partial lipodystrophy, severe insulin resistance and dyslipidemia. PLAAT3-deficient WAT showed a failure to liberate arachidonic acid (AA) from membrane phospholipids resulting in an inactive gene network downstream of adipogenesis master regulator and anti-diabetic drug target PPARG. These findings establish PLAAT3 deficiency in humans as a novel type of partial lipodystrophy due to an AA- and PPARG-dependent defect in WAT differentiation and function.

Partial isolation and function of the prostacyclin regulating plasma factor

1985 ◽  
Vol 69 (4) ◽  
pp. 383-393 ◽  
Author(s):  
H. Deckmyn ◽  
C. Zoja ◽  
J. Arnout ◽  
A. Todisco ◽  
F. VANDEN Bulcke ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Reduced Glutathione ◽  
Physiological Role ◽  
Plasma Factor ◽  
High Concentrations ◽  
Partial Isolation ◽  
Glutathione Cycle ◽  
And Function ◽  
Plasma Activity

1. Rat aortic rings stop producing prostacyclin upon prolonged washing in buffer. This ‘exhaustion’ is caused by inhibition of cyclo-oxygenase, since these rings still convert cyclic endoperoxides but not arachidonic acid into prostacyclin, and most probably is due to high concentrations of peroxides: it can be accelerated by H2O2 or by interrupting the glutathione cycle, while it is delayed by reduced glutathione. 2. Incubation of exhausted rings in human plasma or in a plasma filtrate restores to some extent prostacyclin formation. This filtrate, in particular from uraemic subjects, also inhibits the H2O2 initiated oxidation of guaiacol by ram seminal vesicle microsomes or horseradish peroxidase. 3. The prostacyclin regulating plasma factor has been partially purified and identified as a stable and very polar molecule of mol. wt. 300–400, able to reactivate prostacyclin generation by exhausted rings. We suggest that one or more low mol. wt. plasma components prolong vascular prostacyclin formation by acting as reducing cofactor for cyclo-oxygenase peroxidase. 4. The main physiological role of this plasma activity is probably to protect the vascular prostacyclin forming system from exhaustion during persistent irritation.

Evidence for two-pore domain potassium channels in rat cerebral arteries

2006 ◽  
Vol 291 (2) ◽  
pp. H770-H780 ◽  
Author(s):  
Robert M. Bryan ◽  
Junping You ◽  
Sharon C. Phillips ◽  
Jon J. Andresen ◽  
Eric E. Lloyd ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Metabolic Pathways ◽  
Cerebral Arteries ◽  
Inward Rectifier ◽  
Rt Pcr ◽  
Independent Mechanism ◽  
Induced Currents ◽  
And Function ◽  
Pore Domain

Little is known about the presence and function of two-pore domain K+ (K2P) channels in vascular smooth muscle cells (VSMCs). Five members of the K2P channel family are known to be directly activated by arachidonic acid (AA). The purpose of this study was to determine 1) whether AA-sensitive K2P channels are expressed in cerebral VSMCs and 2) whether AA dilates the rat middle cerebral artery (MCA) by increasing K+ currents in VSMCs via an atypical K+ channel. RT-PCR revealed message for the following AA-sensitive K2P channels in rat MCA: tandem of P domains in weak inward rectifier K+ (TWIK-2), TWIK-related K+ (TREK-1 and TREK-2), TWIK-related AA-stimulated K+ (TRAAK), and TWIK-related halothane-inhibited K+ (THIK-1) channels. However, in isolated VSMCs, only message for TWIK-2 was found. Western blotting showed that TWIK-2 is present in MCA, and immunohistochemistry further demonstrated its presence in VSMCs. AA (10–100 μM) dilated MCAs through an endothelium-independent mechanism. AA-induced dilation was not affected by inhibition of cyclooxygenase, epoxygenase, or lipoxygenase or inhibition of classical K+ channels with 10 mM TEA, 3 mM 4-aminopyridine, 10 μM glibenclamide, or 100 μM Ba2+. AA-induced dilations were blocked by 50 mM K+, indicating involvement of a K+ channel. AA (10 μM) increased whole cell K+ currents in dispersed cerebral VSMCs. AA-induced currents were not affected by inhibitors of the AA metabolic pathways or blockade of classical K+ channels. We conclude that AA dilates the rat MCA and increases K+ currents in VSMCs via an atypical K+ channel that is likely a member of the K2P channel family.

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