Effects of COX-1 and COX-2 inhibitors on eicosanoid biosynthesis and the release of substance P from the guinea-pig isolated perfused lung

2001 ◽  
Vol 50 (1) ◽  
pp. 50-53 ◽  
Author(s):  
R. Amann ◽  
R. Schuligoi ◽  
B.A. Peskar
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Isolated Perfused Lung ◽  
Perfused Lung ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Involvement of cyclooxygenase 2 (COX-2) in intrinsic tone of isolated guinea pig

1995 ◽  
Vol 73 (11) ◽  
pp. 1561-1567 ◽  
Author(s):  
L. Charette ◽  
C. Misquitta ◽  
J. Guay ◽  
D. Riendeau ◽  
T. R. Jones
Keyword(s):  
Guinea Pig ◽  
Time Course ◽  
Cyclooxygenase 2 ◽  
Maximal Response ◽  
Pharmacological Agents ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Indomethacin and related nonsteroidal anti-inflammatory drugs relax prostanoid-dependent intrinsic tone of isolated guinea pig trachea by inhibiting cyclooxygenase (COX). Recently, a second isoform of COX (COX-2) was discovered, which differed from COX-1 with respect to protein structure, transcriptional regulation, and susceptibility to inhibition by pharmacological agents. It is now known that indomethacin nonselectively inhibits COX-1 and COX-2, whereas NS-398 is a selective inhibitor of COX-2. In the present study we compared the activity of a selective (NS-398) and nonselective (indomethacin) COX-2 inhibitor on intrinsic tone of isolated guinea pig trachea. NS-398 ≥ indomethacin produced a reversal of intrinsic tone with a similar concentration-dependent (10 nM to 1 μM) time course (Tmax approximately 20–45 min), potency (EC50 1.7 and 5.6 nM, respectively), and maximal response. Contractions to cholinergic nerve stimulation (45 V, 0.5 ms, 0.1–32 Hz) and histamine were similarly modulated in tissues relaxed with the selective or nonselective COX-2 inhibitors. Immunoblot analyses showed that COX-2 protein synthesis was induced in both the cartilage and smooth muscle portions of the trachea during changes in intrinsic tone. These findings are consistent with pharmacological results and provide the first demonstration that prostanoid tone in isolated guinea pig trachea is dependent on COX-2 activity. The results also suggest that the activity of indomethacin in this preparation is likely related to COX-2 inhibition.Key words: cyclooxygenase 2, relaxation, guinea pig trachea, cyclooxygenase 1.

Capsaicin-induced bronchoconstriction and neuropeptide release in guinea pig perfused lungs

1990 ◽  
Vol 68 (4) ◽  
pp. 1679-1687 ◽  
Author(s):  
F. Kroll ◽  
J. A. Karlsson ◽  
J. M. Lundberg ◽  
C. G. Persson
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Repeated Administration ◽  
Axon Reflex ◽  
Neuropeptide Release ◽  
Pulmonary Vasoconstriction ◽  
Isolated Perfused Lung ◽  
Calcitonin Gene ◽  
Perfused Lung ◽  
The Relationship

In the guinea pig isolated perfused lung, we have examined the relationship between the effects of capsaicin and neuropeptide release and the possible existence of an axon reflex arrangement. Bolus injections into the pulmonary artery of capsaicin (1-100 pmol), substance P (10-1,000 pmol), and neurokinin (NK) A (10-100 pmol) produced a concentration-dependent bronchoconstriction, whereas calcitonin gene-related peptide (CGRP, 20-40 nmol) was without effect. Repeated administration of capsaicin at 40- to 60-min intervals was not associated with tachyphylaxis. These data support the presence of a NK2- (or NKA) type of tachykinin receptor in the guinea pig airways. Tetrodotoxin (0.3-3 microM) inhibited the effect of capsaicin, indicating that an axon reflex was operant. Capsaicin increased overflow of CGRP-like immunoreactivity (-LI) and NKA-LI, the latter only during concurrent infusion of the enkephalinase inhibitor phosphoramidon (3 microM). Phosphoramidon also increased overflow of CGRP-LI, suggesting that both NKA and CGRP were catabolized by a similar enzyme. The purine nucleoside adenosine did not cause any detectable overflow of CGRP-LI, indicating that neuropeptides may not be involved in adenosine-evoked bronchoconstriction and that bronchoconstriction per se does not induce neuropeptide overflow. Capsaicin and NKA had only minor effects on buffer flow, whereas substance P produced pulmonary vasoconstriction. These data clearly demonstrate that capsaicin acts via an axon reflex in the guinea pig airways. Supramaximal concentrations of capsaicin are needed to detect neuropeptide overflow, but the possibility exists that released neuropeptides mediate its effects.

Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus

1999 ◽  
Vol 276 (3) ◽  
pp. R913-R921 ◽  
Author(s):  
Ronald I. Clyman ◽  
Pierre Hardy ◽  
Nahid Waleh ◽  
Yao Qi Chen ◽  
Françoise Mauray ◽  
...  
Keyword(s):  
Significant Role ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Relative Contribution ◽  
Cox Inhibitor ◽  
Fetal Lamb ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2 synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.

New indomethacin analogs as selective COX‐2 inhibitors: Synthesis, COX‐1/2 inhibitory activity, anti‐inflammatory, ulcerogenicity, histopathological, and docking studies

2020 ◽  
Author(s):  
Khaled R. A. Abdellatif ◽  
Eman K. A. Abdelall ◽  
Heba A. H. Elshemy ◽  
El‐Shaymaa El‐Nahass ◽  
Maha M. Abdel‐Fattah ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Docking Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

scholarly journals Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents

2018 ◽  
Vol 47 (12) ◽  
pp. 4341-4351 ◽  
Author(s):  
Victoria Obermoser ◽  
Daniel Baecker ◽  
Carina Schuster ◽  
Valentin Braun ◽  
Brigitte Kircher ◽  
...  
Keyword(s):  
Antitumor Agents ◽  
Tumor Cell Lines ◽  
Growth Inhibitory ◽  
Cox 2 ◽  
Alkyne Complexes ◽  
Inhibitory Potential ◽  
Cox 2 Inhibitors ◽  
Ht 29 ◽  
Cox 1 ◽  
Mcf 7

Chlorine-substituted [(prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl complexes are selective COX-2 inhibitors with growth-inhibitory potential against COX-1/2 containing MDA-MB-231 and HT-29 tumor cell lines. The metabolic activity of non-tumorigenic HS-5 cells and COX-1/2-independent MCF-7 cells is not influenced.

scholarly journals Synthesis of Novel Benzodifuranyl; 1,3,5-Triazines; 1,3,5-Oxadiazepines; and Thiazolopyrimidines Derived from Visnaginone and Khellinone as Anti-Inflammatory and Analgesic Agents

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 220 ◽  
Author(s):  
Ameen Ali Abu-Hashem ◽  
Sami A Al-Hussain ◽  
Magdi E. A. Zaki
Keyword(s):  
Sodium Ethoxide ◽  
Standard Drug ◽  
Chemical Structures ◽  
Cyclooxygenase 1 ◽  
Analgesic Agents ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
New Compounds ◽  
Cox 2 Inhibitors ◽  
Cox 1

Novel (4-methoxy or 4,8-dimethoxy)-3-methyl-N-(6-oxo-2-thioxo-1,2,3, 6-tetrahydro- pyrimidin-4-yl) benzo [1,2-b: 5, 4-b’] difuran-2-carboxamide (5a–b) has been synthesized by the reaction of visnagenone–ethylacetate (2a) or khellinone–ethylacetate (2b) with 6-aminothiouracil in dimethylformamide or refluxing of benzofuran-oxy-N-(2-thioxopyrimidine) acetamide (4a–b) in sodium ethoxide to give the same products (5a,b) in good yields. Thus, compounds 5a–b are used as an initiative to prepare many new heterocyclic compounds such as 2-(4-(3-methylbenzodifuran- 2-carbox-amido) pyrimidine) acetic acid (6a–b), N-(thiazolo[3, 2-a]pyrimidine)-3-methylbenzo- difuran-2-carboxamide (7a–b), N-(2-thioxopyrimidine)-methylbenzodifuran-2-carbimidoylchloride (8a–b), N-(2-(methyl-thio) pyrimidine)-3-methylbenzodifuran-2-carbimidoylchloride (9a–b), N-(2, 6 -di(piperazine or morpholine)pyrimidine)-1-(3-methylbenzodifuran)-1-(piperazine or morpholine) methanimine(10a–d), 8-(methylbenzodifuran)-thiazolopyrimido[1,6-a][1,3,5]triazine-3,5-dione (11a –b), 8-(3-methyl benzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-trione (12a–b), and 2,10 -di(sub-benzylidene)-8-(3-methylbenzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-3,5,11- trione (13a–f). All new chemical structures were illustrated on the basis of elemental and spectral analysis (IR, NMR, and MS). The new compounds were screened as cyclooxygenase-1/ cyclooxygenase-2 (COX-1/COX-2) inhibitors and had analgesic and anti-inflammatory activities. The compounds 10a–d and 13a–f had the highest inhibitory activity on COX-2 selectivity, with indices of 99–90, analgesic activity of 51–42% protection, and anti-inflammatory activity of 68%–59%. The inhibition of edema for the same compounds, 10a–d and 13a–f, was compared with sodium diclofenac as a standard drug.

Aggravation by Selective COX-1 and COX-2 Inhibitors of Dextran Sulfate Sodium (DSS)-Induced Colon Lesions in Rats

2007 ◽  
Vol 52 (9) ◽  
pp. 2095-2103 ◽  
Author(s):  
Mitsuaki Okayama ◽  
Shusaku Hayashi ◽  
Yoko Aoi ◽  
Hikaru Nishio ◽  
Shinichi Kato ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Effects of COX-1 and COX-2 inhibitors on the firing of rat midbrain dopaminergic neurons—Possible involvement of endogenous kynurenic acid

Synapse ◽  
2006 ◽  
Vol 59 (5) ◽  
pp. 290-298 ◽  
Author(s):  
Lilly Schwieler ◽  
Sophie Erhardt ◽  
Linda Nilsson ◽  
Klas Linderholm ◽  
Göran Engberg
Keyword(s):  
Dopaminergic Neurons ◽  
Kynurenic Acid ◽  
Midbrain Dopaminergic Neurons ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1
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