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Cyclooxygenases (Cox-1, Cox-2,
and Cox-3) Antibodies
Prostanoids sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. The prostanoid family includes PGD2, PGE2, PGF2alpha, PGI2, thromboxane A2 and prostaglandins. The prostaglandins (PGs) are implicated in various physiological and pathophysiological events, including male fertility, menstruation, ovulation, pregnancy, implantation and inflamatory and neoplastic diseases. The biosynthesis of PGs and some other prostanoids, is catalyzed in a rate limiting step by PG-H synthase (also known as cyclooxygenase (COX), PG-endoperoxidase synthase (PTGS)) which converts arachiodonic acid to prostaglandin/prostanoid precursor PGH2. Two cyclooxygenase isozymes, COX1 (human, 576aa, 69-72kDa; chromosome 9) and COX2 (human, 604aa, 74 kDa; chromosome 1) have been identified. COX1, a constitutively expressed isoform, produces physiologically relevant prostanoids such as those in stomach and platelets. COX2 isoform is inducible and rapidly upregulated at inflamation sites and forms proinflamatory prostanoids. The overexpression of COX-2 also leads to tumerogenesis. Recently, a third isoform COX3 (canine 633aa; ~65kDa in human aorta) has been reported. Two smaller COX1-derived proteins (partial COX1) PCOX1a (canine 414aa, ~53kDa in human aorta) and PCOX1b have also been characterized. The COX3, but not PCOX1a, possesses glycosylation-dependent cyclooxygenase activity. The nonsteroidal antiinflammatory drugs (NSAIDs) reduce the formation of prostaglandins by inhibiting the activity of cyclooxygenases (COX1, COX2 and COX3), This ability was associated with inhibition of COX, which converts arachidonic acid to the prostaglandin precursor prostaglandin H2. COX1: It consists of 70kD subunits which are constitutively expressed and are involved in a range of physiological functions, Inhibition of gastric expressed COX-1 resulted in most of the unwanted side effects. Non-steroidal inflammatory drugs(NSAIDs) treated the symptoms. The anti COX1 antibodies were produced in rabbits by immunizing them with ram seminal vesicles which has no cross reacitivity to COX2. COX2: It is a 74 kD protein having 60% homology with COX1, expressed by extracellular stimuli such as tumor promoters, pro-inflamatory cytokines, mitogensand oncogenes in different cells. The control of COX2 gene expression is regulated at the level of transcriptional and post-transcriptional mechanisms. COX3: It has an insert of 30-34aa in the signal sequence of COX1, this signal peptide is cleaved in COX1 and COX2 but it is retained in COX3 and PCOX1a. The antibodies produced for the above peptides will be specific only for COX3 and PCOX1a. Human COX3 mRNAs are abundant in cerebral cortex and heart. The COX3 activity is selectively inhibited by analgesic/antipyretic drugs such as acetaminophen, phenacetin, antipyrine etc and is potently inhibited by some nonsteroidal anti-inflammatory drugs. Thus inhibition of COX3 could represt a primary central mechanism by which these drugs ease pain and fever.
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