Prostaglandin E series

Figure 11.26 The structures of the prostaglandin E series produced from three polyunsaturated fatty acids containing 20 carbon atoms but a different number of double bonds. The number of double bonds in the three different acids produces prostaglandins of the E series with a different number of double bonds outside the cyclopentane ring. It is this number which influences the function of the prostaglandin and similarly the function of prostacyclins and thromboxanes (see text). Note, PGEi has one double bond, PGE2 has two double bonds and PGE3 has three double bonds outside the cyclopentane ring.

Because renal vasodilatation and hyperfiltration are often associated with a natriuretic response, a number of activators or inhibitors of endogenous vasoactive systems can cause increased NaCl excretion, and some of these may be developed into compounds of clinical interest in special situations. Such agents include natriuretic pqDtides most notably B-type natriuretic peptide (nesiritide), neutral endopeptidase (NEP) inhibitors (thiorphan, phosphoramidon), mixed NEP and ACE inhibitors (omapatrilat), guanylin and uroguanylin, kinins, prostaglandins of the E series, adrenomedullin, relaxin, prolactin, and others. 

For instance, the marked lack of stability of prostaglandins of the E series (26). [20] in acid as well as in basic medium, is due to the presence of a 3-hydroxyketone system in the structure which, under these conditions, is dehydrated to give in the first place the secondary prostaglandins of the A series (26a) and later on, under more drastic conditions, the prostaglandins of the B series (26b) (Scheme 4.6). 

According to these heuristic principles, a possible synthesis of prostaglandins that proceeds via an aldol condensation in the last step, would be in principle valid for synthesis of prostanoids of the A and the B series (26a or 26b). but not for those of the E series owing to the great unstability of the resulting aldol (P-hydroxyketone or 1,3-C system) under the reaction conditions [20] (Scheme 4.7). 

MS and GC-MS. A variety of derivatives have been used to protect labile functional groups of the free prostaglandins prior to gas chromatography and direct fragmentation in GC-MS. The 9,11-/3-ketol grouping of the E series is particularly sensitive in vapour phase analysis and commonly 0-methyloxime TMS ether derivatives or O-methyloxime acetates have been employed in GC-MS (e.g. [426]). An alternative approach is to dehydrate the ketol under controlled conditions to the more stable enone analogues of the B series [427,428]. The cyclic n-butylboronate of the 9,11-diol in the F series when used with methyl ester TMS ethers confers good GC properties and some simplification in... 

Calabrese JR, Skwerer RG, Bama B, Gulledge AD, Valenzuela R, Butkus A, Subichin S, Krupp NE (1986) Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Res 17 41-47. 

It should be noted that, whereas most of the agonists described at EP, receptors are obvious derivatives of PGE2 (with the exception of iloprost), none of the antagonists thus far described bear any clear chemical resemblance to E series prostaglandins. 

Prostaglandins - Several reports indicate that the products of arachi-donic acid metabolism, i.e., prostaglandins, prostacyclins and thromboxanes are involved in the pathophysiology of obstructive lung disease.Prostaglandins of the E series are bronchodilators while prostaglandins of the F series are bronchoconstrictors. 

Tocher DR, Bell JG, Femdale BM, Sargent JR. Effects of dietary gamma-linolenic acidrich borage oil combined with murine fish oils on tissue phospholipid fatty acid composition and production of prostaglandins E and F of the 1-, 2-, and 3-series in a marine fish deficient in delta 5 fatty acyl desaturase. Prostagland Leukotr Essent Fatty Acids 1997b 57 125-34. 

Certain prostaglandins have opposite effects in different organs, that is, their receptors are tissue-specific. (For example, several E-series prostaglandins cause smooth muscle relaxation in organs such as the intestine and uterus. The same molecules promote contraction of the smooth muscle in the cardiovascular system.)... 

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