scholarly journals Possible role of thromboxane A2 in basal tone and contractile response to arachidonic acid in isolated canine cerebral artery

1986 ◽  
Vol 40 ◽  
pp. 263
Author(s):  
Hiroaki Shirahase ◽  
Hachiro Usui ◽  
Kazuyoshi Kurahashi ◽  
Motohatsu Fujiwara
Keyword(s):  
Arachidonic Acid ◽  
Cerebral Artery ◽  
Contractile Response ◽  
Thromboxane A2 ◽  
Basal Tone

Diabetic Retinopathy And Thromboxane Like Substance

1981 ◽  
Author(s):  
M A Lazzari ◽  
M Gimeno ◽  
N M Sutton ◽  
J R Lopez
Keyword(s):  
Diabetes Mellitus ◽  
Arachidonic Acid ◽  
Diabetic Retinopathy ◽  
Risk Factor ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Thromboxane A2 ◽  
Initial Step ◽  
Platelet Activity

Diabetes Mellitus (DM) is a risk factor in the development of vasculopathies and its complications. It produces also its own microangiopathy. Evidence was reported of increased platelet activity in DM in different assays. Platelets aggregation and the arachidonic cycle could play a key role in the increased tendency to thrombosis. A disorder of ratio TXA2/PGI2, two opposing prostaglandin derivatives, could be the initial step. We intended to evaluate a thromboxane like substance (TLS) produced from platelet rich plasma (PRP) and to compare between normals and diabetic retinopathy (DR) patients. TLS was measured in 16 controls and 16 patients. Assay was done with the aggregating activity developed in PRP (considered TLS) after addition of arachidonic acid (f.c. 2 mM). The supernatant of the PRP (100 μl) was taken 40 sec. after the aggregation started and were added to a normal PRP treated with aspirin (f.c. 40 μl/ml) adjusted to 250.000 - 300.000 pl/μl and the degree of platelet aggregation measured in a Chrono Log Aggregometer. TLS was inactivated after its incubation during 2 min. at 37°C. This finding suggests this activity is due to TXA2.The results obtained (expressed in % of platelet aggregation) were: controls x 16.37% ± 6.28 and DR x 36.00% ± 9.72.The increase detected in the DR group supports previous experimental reports suggesting the role of the thromboxane A2 in vaso occlusive complication of diabetes mellitus.

ADRENALINE (ADR) INTERACTIONS WITH THROMBIN AND COLLAGEN -EFFECTS ON PLATELET ARACHIDONATE RELEASE AND 5HT SECRETION AND ROLE OF ENDOGENOUSLY FORMED THROMBOXANE A2 (TxA2)

1987 ◽  
Author(s):  
Y Patel ◽  
S Krishnamurthi ◽  
V V Kakkar
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenylate Cyclase ◽  
Synergistic Effects ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Presence And Absence ◽  
Pre Treatment ◽  
Arachidonate Release

We have examined the effect of combinations of ADR + thrombin (T) and ADR + collagen (C) on platelet arachidonate release and 5HT secretion, and assessed the role of endogenously formed TxA2 on these responses using indomethacin (I). Washed, human platelets prelabelled with [3H]-arachidonic acid (AA) or [14C]-5HT were used, ADR was added 10 sec before T or C and the reaction was terminated 3 min later. In the range 1-100μM, ADR induced no detectable aggregation or 5HT secretion but potentiated platelet aggregation when added with sub-threshold concentrations of T or C, which on their own induced no aggregation. At 2-4 fold higher concentrations of T and C (threshold for 5HT secretion), 5HT secretion and AA/TXB2 release were also potentiated by ADR (1-10μM) by 30-50%. Pre-treatment of platelets with I (10μM) abolished threshold T and C-induced 5HT secretion, as well as its potentiation by ADR. However, approximately 2-fold and 5-fold higher concentrations of T and C respectively were able to induce 'I-insensitive'secretion, which was further potentiated by ADR. In I-treated platelets, C-induced AA release and its potentiation by ADR were also abolished suggesting a role for endogenously formed TxA2 This was confirmed by addition of the TxA2 mimetic, U46619 (0.3μM), which potentiated C-induced AA release in the presence and absence of ADR, even though it induced no AA release on its own or, in combination with ADR alone in the absence of collagen. The latter suggests agonist specificity regarding the ability of TxA2 to synergistically stimulate AA release. Finally, unstirred platelets in PRP pre-incubated with ADR (10μM) for 120 min lost their responsiveness to ADR, when eventually stirred; however, these 'ADR-desensitised' platelets when washed and resuspended, were able to demonstrate synergistic effects on secretion when stimulated with ADR+T or ADR+C. This is analogous to the previously demonstrated ability of ADR to inhibit adenylate cyclase even in 'ADR-desensitised' platelets and re-inforces the separation regarding the mechanisms underlying the various effects of ADR on platelets.

scholarly journals The role of ADP secretion and thromboxane synthesis in factor VIII binding to platelets

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 186-190
Author(s):  
G Di Minno ◽  
SS Shapiro ◽  
PM Catalano ◽  
L De Marco ◽  
S Murphy
Keyword(s):  
Arachidonic Acid ◽  
Factor Viii ◽  
Binding Sites ◽  
Human Platelet ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Prostaglandin Endoperoxide ◽  
Platelet Thromboxane

Following stimulation with arachidonic acid, collagen, U-46619 (a stable analogue of prostaglandin endoperoxide/thromboxane-A2), thrombin, or adenosine diphosphate (ADP), unstirred human platelet suspensions bound labeled factor VIII in a reaction that reached equilibrium within 10 min. Apyrase inhibited binding induced by arachidonic acid, collagen, U-46619, and thrombin by less than 40%, but inhibited ADP-induced binding by 95%. Binding to aspirin-treated platelets was normal in response to U-46619, reduced by 60%-70% in response to ADP, collagen, and thrombin, and absent in response to arachidonic acid. Binding in response to U-46619 was not altered by the combination of apyrase and aspirin. Binding of factor VIII was decreased by 90% when 10 mM EDTA was added before each agonist, but it was inhibited less than 30% when EDTA was added following platelet stimulation. We conclude that arachidonic acid, collagen, and thrombin can expose binding sites for factor VIII independently of released ADP; that Ca++ is required for activation but probably not for binding of factor VIII to platelets; and that platelet thromboxane synthesis plays a major role in the binding of factor VIII to platelets induced by thrombin, ADP, or collagen.

Regulation of Arachidonic Acid-Dependent Ca++ Influx in Human Platelets

1988 ◽  
Vol 59 (01) ◽  
pp. 086-092 ◽  
Author(s):  
Amalia Bosia ◽  
Wolfgang Losche ◽  
Antonella Pannocchia ◽  
Silvia Treves ◽  
Dario Ghigo ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Reduced Glutathione ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Free Calcium ◽  
Selective Blockade ◽  
Adp Receptor ◽  
Cyclic Endoperoxide

SummaryQuin2 was used to study the rise in cytoplasmic free calcium ([Ca++]i) and the role of prostaglandin (PG) endoperoxides/thromboxane A2 (TxA2), reduced glutathione (GSH), ADP and the glycoprotein (GP) Ilb IIIa complex in mediating [Ca++]i rise during àiachidonic acid(AA)induced platelet aggregation. Ca++mobilization, mostly due to an influx across the plasma membrane, is completely inhibited by aspirin and persists after selective blockade of TxA2 synthase by dazoxiben. GSH total depletion causes a complete aggregation block and 90% inhibition of the transient: U-46619, a stable analog of cyclic endoperoxide PGH2, stimulates [Ca++]i transient in aspirintreated or in GSH depleted platelets. ADPscavengers, ATP (which competes for the ADP receptor), and monoclonal antibodies against the GP Ilb IIIa complex reduce AAinduced Ca++ influx. Therefore, PG endoperoxides alone or a PGH2/TxA2 mimetic stimulate Ca++ influx. Synthesis of PGH2 and TxA2 depends on the availability of GSH, which acts as the reducing cofactor for the PG peroxidase activity. ADP and GP II b ill a are regulating factors of AA mediated Ca++ influx during platelet activation.

scholarly journals The role of ADP secretion and thromboxane synthesis in factor VIII binding to platelets

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 186-190 ◽  
Author(s):  
G Di Minno ◽  
SS Shapiro ◽  
PM Catalano ◽  
L De Marco ◽  
S Murphy
Keyword(s):  
Arachidonic Acid ◽  
Factor Viii ◽  
Binding Sites ◽  
Human Platelet ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Prostaglandin Endoperoxide ◽  
Platelet Thromboxane

Abstract Following stimulation with arachidonic acid, collagen, U-46619 (a stable analogue of prostaglandin endoperoxide/thromboxane-A2), thrombin, or adenosine diphosphate (ADP), unstirred human platelet suspensions bound labeled factor VIII in a reaction that reached equilibrium within 10 min. Apyrase inhibited binding induced by arachidonic acid, collagen, U-46619, and thrombin by less than 40%, but inhibited ADP-induced binding by 95%. Binding to aspirin-treated platelets was normal in response to U-46619, reduced by 60%-70% in response to ADP, collagen, and thrombin, and absent in response to arachidonic acid. Binding in response to U-46619 was not altered by the combination of apyrase and aspirin. Binding of factor VIII was decreased by 90% when 10 mM EDTA was added before each agonist, but it was inhibited less than 30% when EDTA was added following platelet stimulation. We conclude that arachidonic acid, collagen, and thrombin can expose binding sites for factor VIII independently of released ADP; that Ca++ is required for activation but probably not for binding of factor VIII to platelets; and that platelet thromboxane synthesis plays a major role in the binding of factor VIII to platelets induced by thrombin, ADP, or collagen.

A formyl peptide contracts guinea pig lung: role of arachidonic acid metabolites

1987 ◽  
Vol 63 (6) ◽  
pp. 2450-2459 ◽  
Author(s):  
S. A. Shore ◽  
N. P. Stimler-Gerard ◽  
E. Smith ◽  
J. M. Drazen
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Thromboxane A2 ◽  
Leukotriene B4 ◽  
Cyclooxygenase Inhibitors ◽  
Lipoxygenase Inhibitor ◽  
Synthesis Inhibitor ◽  
Leukotriene D4 ◽  
Lipoxygenase Inhibitors

We studied the role of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in mediating N-formyl-methionyl-leucyl-phenylalanine- (FMLP) induced contractions of guinea pig lung parenchymal strips. The cyclooxygenase inhibitors indomethacin (10(-5) M) and aspirin (3 X 10(-5) to 10(-4) M), the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) to 3 X 10(-5) M), and the combined cyclooxygenase/lipoxygenase inhibitors 1-phenyl-3-pyrazolidinone (Phenidone) (3 X 10(-5) to 3 X 10(-4) M) and BW 755C (10(-5) to 10(-4) M) each caused a decrease in the maximum force induced by FMLP (Fmax) and an increase in the concentration of FMLP required to produce 50% of Fmax (EC50). The thromboxane synthesis inhibitor imidazole (3 X 10(-3) M) also decreased Fmax. The leukotriene D4 receptor antagonist FPL 55712 (5.7 X 10(-6) to 1.9 X 10(-5) M) increased the EC50 for FMLP, whereas desensitization of lung parenchymal strips to leukotriene B4 by pretreatment with this leukotriene (10(-7) M) had no effect on FMLP-induced contraction. After exposure to FMLP (10(-6) M), guinea pig lung produced (as determined by high-performance liquid chromatography and radioimmunoassay) leukotrienes C4 and B4, thromboxane A2 (as measured by its stable degradation product thromboxane B2), and prostaglandin F2 alpha. Lung strips not exposed to FMLP showed no evidence of leukotriene production. We conclude that thromboxane A2 and leukotriene C4 generated in response to FMLP mediate a substantial fraction of the force induced by this peptide in guinea pig lung parenchymal strips.

Enteric opioid neurons modulate the basal tone of the isolated puppy ileum

1987 ◽  
Vol 65 (9) ◽  
pp. 1934-1936 ◽  
Author(s):  
T. Neya ◽  
M. Mizutani ◽  
S. Nakayama
Keyword(s):  
Electrical Stimulation ◽  
Longitudinal Muscle ◽  
Contractile Response ◽  
Tonic Contraction ◽  
Spontaneous Motility ◽  
Basal Tone

We studied the role of enteric opioid neurons in the spontaneous motility of the longitudinal muscle in the isolated puppy ileum. Regular fluctuations in tone that rose above and returned to the basal level occurred at an interval of 4.7 ± 0.3 min. Naloxone (10−8 and 10−7 M) reduced the spontaneous tonic contraction by 42.6 ± 11.6% (p < 0.02) and 77.0 ± 3.6% (p < 0.001), respectively. Tetrodotoxin (3.1 × 10−7 M) and atropine (10−7 M) terminated the fluctuations. Met- and Leu-enkephalins (10−9–10−8 M) caused tonic contraction which was abolished by tetrodotoxin and atropine. The contractile response produced by transmural electrical stimulation was reduced by naloxone (10−7 M). This response was also abolished by atropine and tetrodotoxin. These results suggest that enteric opioid neurons are spontaneously active and might operate, at least in part, to raise the basal tone of the longitudinal muscle in the puppy ileum through a cholinergic excitatory mechanism.

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