Selective COX-2 inhibitors, drugs that inhibit PTGS2 (or COX-2, cyclooxygenase-2), are commonly used to reduce inflammation and pain. Drosophila lacks cyclooxygenases and thus can serve as a model to study COX-2-independent mechanisms (and side effects) of these drugs. Using fly models, two different classes of selective COX-2 inhibitors have been shown to have deleterious effects upon ion channels that impact normal cardiac function.
In a larval heart prep, micromolar concentrations of the selective COX-2 inhibitor celecoxib reduced heart rate and induced pronounced arrhythmia. Based on recordings of activity of potassium channels in the larval body wall, it was shown that celecoxib inhibits delayed rectifier Kv2 potassium channels. Animals homozygous for an amorphic mutation in the fly gene Shab, which encodes the structural alpha subunit of a Kv2 delayed rectifier potassium channel, were examined. Assayed as larvae, Shab3 animals exhibit many partial contractile events (similar to fibrillation activity) and arrhythmic heartbeat.
In assays using the larval heart, the selective COX-2 inhibitor SC-791 reduced heart rate without arrhythmia; at higher concentrations, progressively weaker contractions with gradual cessation of heartbeat were observed. These effects of SC-791 appear to be due to inhibition of L-type calcium channels.
[updated Mar. 2018 by FlyBase; FBrf0222196]
Drugs that inhibit PTGS2 (or COX-2, cyclooxygenase-2) are commonly used to reduce inflammation and pain. Drosophila lacks cyclooxygenases and thus can serve as a model to study COX-2-independent mechanisms (and side effects) of these drugs (FBrf0218642).
Cyclooxygenase (also known as COX, Prostaglandin-endoperoxide synthase, Prostaglandin G/H synthase) is encoded by two genes in human. PTGS1 (COX-1) is typically described as the constitutive isoform and PTGS2 (COX-2) as an inducible isoform. Cyclooxygenases catalyze the rate-limiting step of prostaglandin production. [Gene Cards, PTGS2; 2018.03.05]
Moderate-scoring ortholog of human genes KCNB1 and KCNB2; lower-scoring ortholog of many human voltage-gated potassium channel genes (1 Drosophila to many human). Dmel\Shab shares 42-44% identity and 56-57% similarity with KCNB1 and KCNB2.
