CYCLOOXYGENASES 1 AND 2
Tóm tắt
▪ Abstract Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
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Tài liệu tham khảo
Vane JR, 1971, Nature, 231, 232
O'Neill GP, 1994, Mol. Pharmacol., 45, 245
Ristimäki A, 1997, Cancer Res., 57, 1276
Richards JS, 1995, Rec. Prog. Hormone Res., 50, 223
Blatteis CM, 1997, News Physiol. Sci., 12, 1
Cao C, 1997, Am. J. Physiol., 272, R1712
Gardiner NJ, 1997, Br. J. Pharmacol., 120, 71P
Furst DE. 1997. Meloxicam: selective COX-2 inhibition in clinical practice. InSelective COX-2 Inhibitors: Pharmacology, Clinical Effects and Therapeutic Potential, ed. JR Vane, JH Botting. London: Kluwer/William Harvey Press. In press
Lanza F, 1997, Gastroenterology, 112, A194
Lanza FL, 1997, Gastroenterology, 112, A194
Hubbard RC, 1996, J. Invest. Med., 44, 293A
Chan C-C, 1995, J. Pharmacol. Exp. Ther., 274, 1531
Thun MJ, 1996, Cancer Res., 53, 1322
Samaha HS, 1997, Cancer Res., 57, 1301
Ford-Hutchinson AW. 1997. New highly selective COX-2 inhibitors. InSelective COX-2 Inhibitors: Pharmacology, Clinical Effects and Therapeutic Potential, ed. JR Vane, JH Botting. London: Kluwer/William Harvey Press. In press
Parrett ML, 1997, Int. J. Oncol., 10, 503
Thompson HJ, 1997, Cancer Res., 57, 267
Hampel H, 1995, Drug News Perspect., 8, 599
Patrignani P, 1997, J. Physiol. Pharmacol.
Laneuville O, 1994, J. Pharmacol. Exp. Ther., 271, 927
Patrignani P, 1994, J. Pharmacol. Exp. Ther., 271, 1705
Carabaza A, 1996, Prostaglandins Leukot. Essent. Fatty Acids, 55, 93