Prostanoids functions

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

Demling, R.H., Katz, A., Lalonde, C., Ryan, P. and Jin, L-J. (1987). The immediate effect of burn wound excision on pulmonary function in sheep. The role of prostanoids, oxygen radicals and chemoattractants. Surgery 101, 44-55. 

More recently, the prostanoid metabolites of P. homomalla have been reinvestigated relative to their potential natural function [69], A minor new metabolite was isolated and characterized in this work by high field NMR studies. Its structure, the 9-O-acetate of methyl PGF2ar (55), seems secure given the opportunity to compare H and 13C NMR data sets with an earlier isolate of the 11-O-acetate of PGF2c( (56) [70],... 

Hammad H, Kool M, Soullie T, Narumiya S. Trottein F. Hoogsteden HC, Lambrecht BN Activation of the D prostanoid 1 receptor suppresses asthma by modulation of lung dendritic cell function and induction of regulatory T cells. J Exp Med 2007 204 357-367. 

Narumiya, S., and EitzGerald, G. A. (2001) Genetic and pharmacological analysis of prostanoid receptor function. J. Clin. Invest. 108, 25-30. 

Although prostanoids can activate peroxisome proliferator-activated receptors (PPARs) if added in sufficient concentration in vitro, it remains questionable whether these compounds attain concentrations sufficient to function as endogenous nuclear-receptor ligands in vivo. 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

The conversion of oleoyl-CoA to linoleoyl-CoA is accomplished by some insects118 but does not take place in most animals. As a result of this biosynthetic deficiency, polyunsaturated fatty acids such as linoleic, linolenic, and the C20 arachidonic acid are necessary in the diet (Box 21-B). One essential function of linoleic acid is to serve as a precursor of prostaglandins and related prostanoids (Section D). Dietary linoleate is converted to its Co A derivative and then by sequential A6 desaturation,119 elongation, and then A5 desaturation, to the 20 4 (A5 8 11 14) arachidonoyl-CoA (Fig. 21-2, lower right). These acids are referred to as 0)6 because of the position of the last double bond. Linolenic acid can be converted in an analogous fashion to the CoA derivative of the 20 5 (A5 8 11 14 17 co6) eicosapentaenoic acid (EPA). The 22 6 docasahexaenoic acid (DHA Fig. 21-2) is apparently formed by elongation of the 22 5 acyl-CoA to 24 5, desaturation, transfer to a peroxisome or mitochondrion, and p oxidation to shorten the chain.953... 

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