The role of nitric oxide in prostaglandin biology; update

Abstract

The biosynthesis of nitric oxide (NO) and prostaglandin share many similarities. Two major forms of nitric oxide synthase (NOS) and cyclooxygenase (COX) have been identified: constitutive versus inducible. In general, the constitutive form functions in housekeeping and physiologic roles whereas the inducible form is up-regulated by mitogenic or inflammatory stimuli and is responsible for pathophysiological responses. The cross talk between the COX and NOS pathways was initially reported in 1993 and since then, numerous studies have been undertaken to delineate the functional consequences of this interaction as well as the potential mechanism by which each pathway interacts. This review will focus in particular on recent advances in this field that extend our understanding of these two pathways under various systems.

Figure 1. The scheme of COXs enzyme reaction mechanism

Cox enzymes produce PGH2 by two step chemical reactions; cyclooxygenase and peroxidase. PGH2 is further converted to other prostanoid by tissue specific enzymes.

Figure 2. The role of Nitric oxide Synthase (NOS) and Cyclooxygenase

Both enzymes share the similar pathway for activation and their physiological as well as pathophysiological implication.

Figure 3. Proposed mechanisms of NO-mediated regulation of prostaglandin production

Nitric oxide produced by NOS can directly modify cysteine(s) in the COXs and activate it. Moreover, superoxide can be simultaneously generated under the same environment which can enhance NO production. Superoxide rapidly interacts with NO producing peroxynitrite which can interact with either heme or tyrosine residue(s) in COX2.