Advances in Pharmacology, Vol. 35 by J. Thomas August, M.W. Anders, Ferid Murad, Joseph T. Coyle

By J. Thomas August, M.W. Anders, Ferid Murad, Joseph T. Coyle (Eds.)

Each one quantity of Advances in Pharmacology presents a wealthy choice of studies on well timed issues. Emphasis is put on the molecular bases of drug motion, either utilized and experimental.

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See Section 111 for agents which regulate mRNA and protein levels of COX. In addition to differences in structure, substrate specificity, and regulation, it has recently been demonstrated that differences occur in the intracelMar localization of COX-1 and COX-2. The activity of COX-1 is mainly localized to the endoplasmic reticulum, although some activity is observed around the nucleus. , 1994). The discovery of different intracellular localizations in conjunction with factors which affect regulation and different substrate specificities suggests that these two enzymes can act independently.

1994). 2. Cyclo-Oxygenase 2 The COX-2 gene is approximately 60% homologous to COX-1 in human, mouse, and avian species. , 1995). It encodes for a 604 (for mouse) or 603 (for chick) amino acid protein. COX-2 protein has a unique 18 amino acid insert near the carboxyl terminal. Similar to COX-1, the COX-2 protein has an EGF-like domain, a serine site for aspirin acetylation, and five possible glycosylation sites. , 1994). The COX-2 mRNA is approximately 4 kb. , 1991). For details of distribution of COX mRNA in human tissues see O’Neill and Ford-Hutchinson (1993).

Prostaglandins and Pain The PGs alone do not produce pain, but rather sensitize afferent nociceptors to the effects of other pain producing substances such as BK and histamine (Ferreira, 1972; see Fig. 2). The major PGs involved in hyperalgesia are PGE, and PGI,. The hyperalgesic actions of these two mediators are different and point to different pathophysiological roles. , 1975). In contrast, the effects of PGI, are observed more rapidly and quickly decline. , 1978). Differences in the potency and duration of these two prostanoids implicate them in different types of painful conditions.

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