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Compound
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Target Concepts:
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Query: UNIPROT:P00790 (
PGA
)
2,475
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Prostaglandins of the A series have been reported to inhibit tumor cell growth and induce tumor cell differentiation by a yet unknown mechanism. We propose that these effects are due to the presence of a reactive alpha, beta-unsaturated carbonyl group (delta 10,11) in the
cyclopentane
ring of the
PGA
molecule.
PGA
was effective whereas PGB (sterically hindered alpha, beta-unsaturated carbonyl at delta 8, 12) and
PGA
conjugated to glutathione were ineffective. 15-Epi-PGA2 was as effective as PGA2 suggesting that the S absolute configuration of the 15-hydroxyl group is not essential. There was no correlation between generation of cAMP and inhibition of cell proliferation or induction of differentiation by various prostaglandins. The data suggest that
PGA
's and
PGA
-like compounds inhibit tumor cell growth and induce differentation because of the chemical reactivity of the alpha, beta-unsaturated carbonyl rather than hormonal activity of the prostanoid nucleus.
...
PMID:Requirement of a reactive alpha, beta-unsaturated carbonyl for inhibition of tumor growth and induction of differentiation by "A" series prostaglandins. 403 34
Prostaglandins are analogs of the parent 20 carbon prostanoic acid. They are divided into 4 series: PGE; PGF;
PGA
; PGB, according to the presence of functionalities in the
cyclopentane
structure. Biosynthesis of prostaglandins were first independently reported by Bergstrom et.al. and van Dorp et.al. who showed that certain w-6-unsaturated fatty acids were biological precursors of prostaglandins. Later, various investigators reported the biosynthesis of prostaglandins of the different series. The 2 most widely used routes of prostaglandins synthesis are 1) the Corey cyclopentyl-lactone route, and 2) the bicyclohexane route. The synthesis is divided into 1) naturally occuring primary prostaglandins and 2) the prostaglandin analogs and derived prostaglandins. Because of the general instability of natural prostaglandins in the basic and acidic milieu, various preparations of prostaglandins and chemically stable dosage forms have been developed. Various methods used in analyzing prostaglandins include: 1) TLC; 2) GLC; 3) spectral methods; 4) radioimmunoassay; and 5) enzymatic assay. In vitro and in vivo studies on the metabolism and catabolism of various prostaglandins showed that they are rapidly metabolized in various animal systems and humans. The major routes for this metabolic transformation are: 1) oxidation of the secondary C15 hydroxy group; 2) reduction of the C13 double bond; 3) B-oxidation; 4) w-hydroxylation; and 5) w-oxidation. Prostaglandins produce a wide range of biological effects on animal and human systems (the reproductive; gastrointestinal; respiratory; and cardiovascular systems). The biological actions of prostaglandins on animal and human reproductive tissue vary depending on the particular prostaglandin studied and hormonal state of the tissue. Certain prostaglandins can decrease the tonus, frequency, and amplitude of spontaneous contractions of human uterine strips while other prostaglandins can cause contraction of isolated myometrial strips. Prostaglandins are widely used in labor induction; induction of therapeutic abortion; and fertility control. Prostaglandins have also been found to either increase or decrease cyclic AMP; inhibit ADP-induced platelet aggregation; lower blood pressure in animals; affect lipid and carbohydrate metabolism, and prevent adjuvant arthritis.
...
PMID:Prostaglandins. 456 72
Antibodies to prostaglandin were obtained by immunization of rabbits with
PGA
(1),
PGA
(2), and PGE(1), protein conjugates of prostaglandins. The antibodies demonstrated specificity toward both the
cyclopentane
ring and the aliphatic side chains. With the use of these antibodies a highly sensitive radio-immunoassay capable of measuring less than picomolar amounts of PGA1, PGA2, and PGE1 has been developed.
...
PMID:Radioimmunoassay for prostaglandins. 553 3