Page 44 - 74_04
P. 44

M. FRESNO Y COLS.  AN. R. ACAD. NAC. FARM

present in mast cells, basophils, and in a subset of T helper cells (Th2)
and may play a role in allergy (36). The lipocalin–type PGD synthase is
mostly expressed in brain and it is especially abundant in the
cerebrospinal fluid (37). Interestingly, PGD2 can be further metabolized
by dehydration to PGJ2, delta12-PGJ2, and 15- deoxy-delta(12,14)-PGJ2,
which is a ligand for the nuclear transcription factor peroxisomal
proliferator activated receptor (PPAR)-gamma having anti-inflammatory
activity (38).

        PGF2a can be synthesized from PGH2 by PGH 9-11-endoperoxide
reductase or PGF synthase (PGFS). In addition it can be generated from
PGE2 by PGE 9-ketoreductase or from PGD2 by PGD-11-ketoreductase
(39).

        Prostacyclin, PGI2, is produced by the action of PGI synthase
(PGIS) which can be induced by mechanical stress, via activation of AP-1
(40).

        TXA2 is synthesized from PGH2 by thromboxane synthase (TXS),
which is constitutively expressed in platelets as well as other blood cells
and various tissues as kidney, lung, liver and placenta. Its regulation takes
place mainly at the transcriptional level (41).

                         PROSTANOID RECEPTORS

        Prostanoids actions, with the possible exception of cyclopentenone
PGs, are mediated through cell surface receptors. These are cell seven
membrane spanning G-protein coupled receptors that are classified into
five basic types, named according to their ligands: DP for PGD2, EP for
PGE2, FP for PGF2, IP for PGI2, and TP for TXA2 (6, 42).

        DP (also named DP1) is weakly expressed in brain despite the
important action of PGD2 in this organ. It is moderately expressed in the
ileum with very weak expression in the lung. DP2, also called CRTH2
(chemoattractant receptor-homologous molecule expressed on Th2 cells),
is expressed on Th2 immune cells being a chemoattractant receptor for
Th2 lymphocyte subset in allergic inflammation (43).

        FP is most abundantly expressed in the corpus luteum according to
the role played by PGF2a in menstrual cycle. It is also expressed in the

8
   39   40   41   42   43   44   45   46   47   48   49