3-Series prostaglandins

Amphibians differ in three important ways from mammals with respect to synthesis of eicosanoids (i) they have EPA as a natural substrate, and thus can potentially produce 3-series prostaglandins and 5 series leukotrienes without dietary supplementation (ii) nucleated erythrocytes and thrombocytes produce cyclooxygenase and lipoxygenase products endogenously and (iii) synthesis of eicosanoids is regulated, at least in part, by environmental temperature. These differences impact the actions of eicosanoids in the cardiovascular system of amphibians. 

The 1- and 3-series prostaglandins are anti-inflammatory and inhibit platelet aggregation, whereas the 2-series are pro-inflammatory and pro-aggregatory.The 1- and 3-series thromboxanes mildly stimulate platelet aggregation and stimulate the contraction of respiratory, intestinal and vascular smooth muscle, as do the leukotrienes. The 2-series thromboxanes have a much more powerful action in this respect. 

Yang, P, Felix, E, Madden, T, Fischer, SM and Newman, RA (2002) Quantitative high-performance liquid chromatography/electrospray ionization tandem mass spectrometric analysis of 2- and 3-series prostaglandins in cultured tumor cells. Anal Biochem, 308,168-177. 

The roles of EPA and DHA in cells include the regulation of eicosanoid production from arachidonic acid (AA 20 4n-6), in that EPA competes with AA to produce various eicosanoids such as the 3-series prostaglandins, prostacyclin, and thromboxane, and the 5-series leukotrienes (LT) and lipoxins. EPA and DHA lower plasma TAG levels and blood pressure (De Deckere et al, 1998 Mori etal, 1999) and regulate ion flux in cardiac cells (Kang and Leaf, 2000). There have been successful trials of secondary prevention of myocardial... 

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

Ellman utilized the Suzuki coupling twice between a support-bound vinyl bromide and an alkyl 9-BBN derivative in a solid-phase synthesis of E- and F-series prostaglandins. The Suzuki reaction was performed in situ, with the hydroboration of a terminal olefin being followed by the palladium-mediated step. This sequence is attractive in library synthesis because of the wide range of suitable commercially available alkenes. The inspiration behind this chemistry was the solution-phase work of Johnson and Braun, where the couplings of 35 with 2-iodo-4-(silyloxy)cyclopent-2-enone 36 went well at room temperature with PdCljCdppO-AsPhj as catalyst (Scheme 41). The modular chemistry demonstrated in this paper was clearly amenable to adaptation to a solid-phase strategy. 

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. 

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.)... 

The E series and series prostaglandins were the first eicosanoids to be characterized chemically and research in the prostaglandin area focused on these compounds until the mid 1970s. It was then that thromboxane A2 and prostacyclin (PGI2) were discovered as relatively labile products of the arachidonate cascade in human platelets and bovine aorta respectively. 

Other commonly used silylation mixtures, e.g. HMDS/ TMCS/pyridine, 8SA/pyridine, 8SA/acetonitri]e/pyri-dine, 8STFA/pyridine and TMSIM/pyridine, also yield niixtures of reaction products [120,121]. The production of 8 series prostaglandins through enolization of A... 

As shown in Table I, the excretion of PGF-M in these patients was comparable to that of normal subjects (13). The Peak Expiratory Flow Rate (PEFR) values increased steadily over the course of 5 days of treatment with steroids and 3-adrenergic agonists, while the PGF-M excretion remained unchanged. PGF-M is a known urinary metabolite of F, D and E series prostaglandins (9,14,15). Thus it would appear from the results in Table I that there was no elevation in the biosynthesis of F, D or E prostaglandins associated with the bronchial asthma of these particular subjects. However, one cannot corpletely dismiss the possibility that, for example, decreased biosynthesis of PGE was balanced by an increased production of PGF. 

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