Cox2

The possible role of eicosanoids in cyclical ovarian function. Size and typing of arachidonic acid metabolites represents the importance of the particular eicosanoid according to current knowledge. Ovulation is the liberation of the mature oocyte from the Graafian follicle. This process is triggered shortly after the mid-cycle luteotropic hormone (LH) surge by the complementary action of LH and follicle-stimulating hormone (FSH). It is accompanied by the 'rupture' of healthy tissue...

Oh

*Represents the most advanced stage of development recorded in at least one of the indications listed. Agents MPO, myeloperoxidase AA, arachidonic acid PMA, phorbol myristate. Methods and tests rc, receptor cm, calcium mobilization CD1 lb up., CD1 lb upregulation ct, chemotaxis nd, neutrophil degranulation np, neutropenia ee. ear edema na, neutrophil aggregation ni, neutrophil infiltration. On the basis of these findings, it might be assumed that LTB4 antagonists exhibit anti-inflammatory...

Z335

'oOjNa Anti-thrombotic pa (guinea-pig) IC50 0.32 iM (U) (preclinical) vc IC50 3.1 nM (U) 239 Daltroban, BM-13505, SK& F-96148 Boehringer Mannheim, Germany Sulotroban, BM-13177, SK& F-95587 Boehringer Mannheim, Germany oq,h Anti-thrombotic pa (guinea-pig) pKb 7.11 (U) asthma ao (guinea-pig) pKb 7.23 (U) (phase III, psc (guinea-pig) ec50 > 10 nM 241 discontinued) pa (rabbit) ic50 0.36 (tM (U) 242 .0___QOjH Anti-thrombotic pa (guinea-pig) pKB 5.80 (U) asthma ao (guinea-pig) pKB 5.96 (U)...

Menstruation

Menstruation is an event restricted to humans and subhuman primates, in which uterine bleeding and contractions occur. Menstruation describes a catabolic process. This process is triggered by functional interactions between the central nervous system, the hypothalamus-pituitary gland and the ovaries. The first menstruation (menarche) occurs between the ages of 9 and 17 years and the last menstruation (menopause) between the age of 45 and 55 years. Background information about cyclical...

Info

Rc (guinea-pig lm) Ki 637 nM (LTD4) 334 be (LTD4) 4.6-6.1-fold shift in ltd4 be dose-response curve following a 400 mg oral dose 335 , Small effects in different asthma models (exercise 336 , cold air induced 337 ). Improves in a 6 week study lung function and some symptoms of mild asthmatics 338 . Venzair , verlukast, L-688,019, MK 679 Merck, USA Venzair , verlukast, L-688,019, MK 679 Merck, USA rc (guinea-pig lm) IC50 3.1 nM (ltd4) to (guinea-pig) pKB 8.8 (ltd4) 340 Aspirin-induced be is...

Biological activity of leukotrienes in the kidney

Cysteinyl leukotrienes are potent constrictors of vascular smooth muscle. Systemic administration of cysteinyl leukotrienes in the rat leads to a reduction in renal blood flow and the glomerular filtration rate 101 . Infusion of LTD4 into the afferent glomerular artery augmented post-glomerular efferent arteriolar resistance, similar to the action of angiotensin II, thus reducing renal blood flow 102 . The reduced glomerular capillary ultrafiltration coefficient was attributed to the effects of...

Bisallylic hydroxylation and hydroxylation with double bond migration

It was obvious that biosynthesis of cis-trans conjugated HETEs by cytochromes P-450 likely involved abstraction of a bisallylic hydrogen in analogy with the oxygenation mechanism of lipoxygenases (see Sections 1.3 and 5.2). Abstraction of hydrogen from the bisallylic methylene carbon requires at least 10 kcal mol less energy than abstraction of allylic or methyl hydrogens 78 , Hydrogen abstraction is often the rate-limiting step in cytochrome P-450 catalysis 42 . Linoleic acid was chosen as a...

Labor

Arachidonic acid metabolites are considered important paracrine regulators in human myometrial contractions 148 . PGF2a and PGE2 are potent pharmacological stimulators of uterine contractility, causing labor at any stage of gestation. Other well-known uterotonins are oxytocin, PAF and endothelins. However, the physiological role of PGF2a and PGE2 in myometrial contractions has been questioned, since they caused much weaker contractions than oxytocin and endothelins in vitro 174,175 , Other...

Steric analysis of hydroxy fatty acids

Enantiomers of cis-trans conjugated HETEs and other cis-trans conjugated hydroxy fatty acids can be separated by chiral HPLC on columns with or without derivatization 107 . This used to be the method of choice, but much better separations can often be obtained on Chiralcel OB columns 30 , These Chiralcel columns can also be used for bisallylic metabolites. The enantiomers of 7-HETE, 10-HETE and 13-HETE were at least partly resolved by HPLC on Chiralcel OD 30 , Steric analysis of bisallylic...

Pvd

Pa (human) IC5o 0.64 nM (ADP) pa (rat) ICso 3.2 nM (ADP) 164,165 rc (rat) KF 0.849 (PGI2) Relaxes bovine coronary artery strips 15-20 times more effective than iloprost 165 . Stimulates or inhibits cAMP formation in intact platelets 124 , In healthy volunteers 75 and 100 ig t.i.d. exerts significant antiplatelet and vasodilating effects 166 . Potent inhibitor of tumor metastases in animals 167-169 , Strongly inhibits the number of lung metastases in the SMT 2a and 13762 MTLn3 mammary carcinomas...

Prostanoid synthases

Arachidonic acid (5Z,8Z,llZ,14Z-eicosatetraenoic acid) is a widely distributed constituent of phospholipids in biological membranes. Due to the presence of four Z-configurated isolated double bonds arachidonate can be converted to a variety of oxygenated derivatives since not only can the double bonds be expoxidized but, through the action of lipoxygenases, the two allylic and three bis-allylic CH-bonds can form peroxides which again can be reduced or isomerized to different classes of...

Hete 11hete 12rhete 15rhete

Formation of eicosanoids by cytochrome P-450-dependent monooxygenation of arachidonic acid. The four pathways which have been identified are shown. They are catalyzed by different cytochrome P-450 isoforms. The hydroxylation with double bond migration (3) resembles the lipoxygenase reaction (see Section 1.3.3 and the scheme on page 12) in that the cis,cis-1,4-pentadiene structure attacked by oxygen isomerizes to an energetically more favorable conjugated cis,trans-1,3-pentadiene...

Eicosanoids and restenosis

The problem of restenosis after endovascular interventions should be mentioned considering the role of eicosanoids in vascular pathology and endothelial function. The introduction of percutaneous transluminal coronary angioplasty (PTCA) by Andreas Gruentzig in 1979 opened new perspectives in the treatment of coronary artery disease. Together with peripheral interventions, implantation of intravascular devices and other endovascular techniques, PTCA is gaining wider and wider clinical...