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VOL. 74 (4) PROSTANOIDS ACTIONS IN CARDIOVASCULAR...

located in the endoplasmic reticulum and nuclear envelope whereas COX-
2 is preferentially expressed around the nuclear membrane (9, 12).

PROSTAGLANDIN AND THROMBOXANE SYNTHASES

Despite the importance of COX isoenzymes in prostanoid
generation, the actual prostanoid profile synthesized by a particular cell
type is determined by the presence of different downstream PG and TX
synthases and isomerases (28) (Figure 1). A particular cell type may
predominantly express a particular isomerase, which will largely
determine which prostanoid is generated. Moreover, some cell types can
express more than one isomerase and a particular COX isoenzyme can
couple to different isomerases in the same cell (29). Thus, COX-1
preferentially couples with Thromboxane synthase (TXS) and PGF2a
synthase (PGFS), while COX-2 is associated to Prostacyclin synthase
(PGIS) and microsomal PGE2 synthase -1 (mPGES-1) (29, 30).
Evenmore, PGH2 and other endoperoxides generated in one cell type may
be secreted and metabolized by isomerases present in surrounding cells
by the so-called “transcellular metabolism” (31).

PGE2 is synthesized by the action of PGE synthases (PGES) of
which there are 3 types: one cytosolic (cPGES) and two membrane-
associated PGE synthases (mPGES)-1 and -2. The (cPGES) belongs to
the glutathione transferase family, is ubiquitously expressed and is
preferentially functionally coupled to COX-1, thus, involved in
housekeeping production of PGE2 (32, 33). In contrast, mPGES-1, which
belongs to the Membrane-Associated Proteins involved in Eicosanoid and
Glutathione metabolism (MAPEG) superfamily, is inducible by similar
stimuli that induce COX-2, being its induction also suppressed by
glucocorticoids. Moreover, mPGES-1 appears functionally coupled with
COX-2 and its induction is usually coordinated with COX-2 (34). A
second type of membrane-bound microsomal PGES is the mPGES-2, able
to couple with both COX isoenzymes, although its functional significance
is still unclear (35).

PGD2 is synthesized from PGH2 by the action of PGD synthases
(PGDS) of which there are two isoforms. The haematopoietic PGDS is

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