Effect of a cyclooxygenase-2 inhibitor on postexercise muscle protein synthesis in humans

Abstract

Nonselective blockade of the cyclooxygenase (COX) enzymes in skeletal muscle eliminates the normal increase in muscle protein synthesis following resistance exercise. The current study tested the hypothesis that this COX-mediated increase in postexercise muscle protein synthesis is regulated specifically by the COX-2 isoform. Sixteen males (23 +/- 1 yr) were randomly assigned to one of two groups that received three doses of either a selective COX-2 inhibitor (celecoxib; 200 mg/dose, 600 mg total) or a placebo in double-blind fashion during the 24 h following a single bout of knee extensor resistance exercise. At rest and 24 h postexercise, skeletal muscle protein fractional synthesis rate (FSR) was measured using a primed constant infusion of [(2)H(5)]phenylalanine coupled with muscle biopsies of the vastus lateralis, and measurements were made of mRNA and protein expression of COX-1 and COX-2. Mixed muscle protein FSR in response to exercise (P < 0.05) was not suppressed by the COX-2 inhibitor (0.056 +/- 0.004 to 0.108 +/- 0.014%/h) compared with placebo (0.074 +/- 0.004 to 0.091 +/- 0.005%/h), nor was there any difference (P > 0.05) between the placebo and COX-2 inhibitor postexercise when controlling for resting FSR. The COX-2 inhibitor did not influence COX-1 mRNA, COX-1 protein, or COX-2 protein levels, whereas it did increase (P < 0.05) COX-2 mRNA (3.0 +/- 0.9-fold) compared with placebo (1.3 +/- 0.3-fold). It appears that the elimination of the postexercise muscle protein synthesis response by nonselective COX inhibitors is not solely due to COX-2 isoform blockade. Furthermore, the current data suggest that the COX-1 enzyme is likely the main isoform responsible for the COX-mediated increase in muscle protein synthesis following resistance exercise in humans.

The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle

“…In skeletal muscle, prostaglandins regulate protein synthesis and degradation after exercise (5,20,23,25) and are necessary for skeletal muscle injury recovery (2,28,29). Prostaglandins are derived from arachidonic acid (AA) via a reaction catalyzed by cyclooxygenase (COX), a ubiquitous enzyme that is expressed in many cell types, including skeletal muscle (31).…”

“…At least two isoforms of COX have been identified, COX-1 and COX-2. Additionally, two variants of COX-1 (COX-1v1 and COX-1v2) have been detected in skeletal muscle (5,39). COX-1 is traditionally viewed as a constitutively expressed protein that primarily has homeostatic functions, while COX-2 is induced by an array of stimuli, including tissue injury (38).…”

“…Skeletal muscle has been shown to express both isoforms of COX (5,31,32,35,39), and both isoforms appear to have an important role in regulating skeletal muscle protein synthesis and degradation (25,26,37). For example, consumption of the COX-inhibiting drugs ibuprofen or acetaminophen inhibits acute exercise-induced increases in skeletal muscle protein synthesis and PGF 2␣ in humans (36,37).…”

“…Additionally, several animal and cell culture studies suggest that COX-2 is essential for skeletal muscle protein synthesis, growth, and tissue repair following injury or pathologies (2,3,16,17,19,28). More recent studies (5,35), however, link the postexercise protein synthetic response to COX-1. Specifically, consumption of a selective COX-2 inhibitor did not inhibit the increase in skeletal muscle protein synthesis (5) after a bout of acute eccentric resistance exercise.…”

“…Together, these data support a hypothesis that COX-1 is the predominant COX enzyme involved in the skeletal muscle response to acute resistance exercise. However, in these previous studies (5,35,39), the activity of the COX enzymes after resistance exercise was not evaluated. Therefore, the purpose of this study was to evaluate skeletal muscle COX enzyme activity after a single bout of resistance exercise.…”