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(EP1, EP2, EP3 and EP4). PGD2, PGF2a, PGI and TXA2 bind to the DP and CRTH2,
FP, IP and TP receptors respectively.

Cyclooxygenases are the target of non-steroidal anti-inflammatory
drugs (NSAIDs). It is generally accepted that these drugs exert their anti-
inflammatory and analgesic actions through inhibition of COX enzymatic
activity. Classic NSAIDs, such as aspirin, inhibit both isoforms at
standard doses. Inhibition of COX-1 may account for some of the
unwanted side effects of these drugs such as gastrointestinal and renal
toxicity. On the other hand, as COX-2 is though to be the predominant
isoform involved in the inflammatory response, the ability of NSAIDs to
inhibit COX-2 activity may explain their therapeutic effects as anti-
inflammatory drugs (Figure 2). Therefore, most of the new research on
anti-inflammatory drugs has been aimed at targeting the COX-2 inducible
production of PGs (8, 20). Newly developed drugs with high selectivity
against COX-2 such as Celecoxib and Rofecoxib have been proved to be
potent anti-inflammatory compounds without causing gastric toxicity
(21).

Many of the functions associated with each COX isoform have
been defined by the therapeutic or adverse effects resulting from
pharmacological inhibition by NSAIDs selective for each isoform.
However, increasing evidence has shown that certain actions of NSAIDs
could be mediated through mechanisms independent of cyclooxygenase
activity and prostaglandin production that may be relevant to their effects
in vivo (22). Thus, extrapolating the role of COX -derived PGs by the use
of COX inhibitors may lead to confusing conclusions. In this sense,
information provided by the use of mice genetically deficient in COX-1
or COX-2 has provided valuable insight into the roles played by those
enzymes in vivo (12, 23, 24). These studies have shown that these two
closely related enzymes have a non-redundant role. Overall, they have
indicated that, contrary to expectations, both, COX-2 and COX-1
participate in the maintenance of normal physiology. In this sense, despite
being mostly inducible, COX-2 deficiency in mice produces dramatic
phenotypic changes related to normal development and in the
maintenance of homeostasis. Thus, COX-2 de?ciency results in a severe
defect in renal development and in reproduction in females (25, 26).

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