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Cyclooxygenases 1 and 2
J R Vane1, Y S Bakhle, R M Botting
1William Harvey Research Institute, St Bartholomew's, London, United Kingdom.
Annual Review of Pharmacology and Toxicology
|May 23, 1998
Summary
Cyclooxygenase-2 (COX-2) is an enzyme involved in inflammation and cell growth. Selective COX-2 inhibitors offer anti-inflammatory benefits without affecting protective prostaglandins, potentially aiding in cancer and Alzheimer's disease treatment.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- Cyclooxygenase (COX) enzymes synthesize prostaglandins (PGs) from arachidonic acid.
- Two isoforms, COX-1 and COX-2, exist with distinct roles and regulation.
- COX-1 produces protective PGs for gastric and renal function, while COX-2 is inducible and linked to inflammation and cell growth.
Purpose of the Study:
- To elucidate the distinct functions and characteristics of COX-1 and COX-2.
- To highlight the therapeutic potential of selective COX-2 inhibition.
Main Methods:
- Enzyme purification and cloning of COX isoforms.
- Analysis of gene induction and substrate/inhibitor selectivity.
- Investigating the physiological roles of COX-1 and COX-2.
Main Results:
- COX-2 is inducible by inflammatory stimuli and growth factors.
- COX-1 and COX-2 exhibit differences in substrate selectivity and cellular localization.
- COX-2 plays roles in pain, fever, ovulation, and birth.
Conclusions:
- Selective COX-2 inhibitors can reduce inflammation while preserving protective PGs.
- These inhibitors show promise for treating inflammatory conditions, colon cancer, and Alzheimer's disease.