Mechanical stimulation of skeletal muscle increases prostaglandin F2α production, cyclooxygenase activity, and cell growth by a pertussis toxin sensitive mechanism

Abstract

Repetitive mechanical stimulation of differentiated skeletal muscle in tissue culture increased the long‐term production of prostaglandin F_2α, an anabolic stimulator of myofiber growth. Within 4 h of initiating mechanical stimulation, the enzymatic activity of cyclooxygenase (prostaglandin GH synthase [PGHS]), a regulatory enzyme in prostaglandin synthesis, was increased 82% (P <.005), and this increase was maintained for at least 24 h. Kinetic analysis of stretch‐activated cyclooxygenase activity indicated a two to threefold decrease in the enzyme's K_m, with little change in its V_max. Immunocytochemical analysis of the cell cultures indicated the presence of high levels of the mitogen‐inducible isoform of cyclooxygenase (PGHS‐2) in the skeletal myofibers compared to the interstitial fibroblasts. While the stretch‐induced increase in cyclooxygenase enzymatic activity was not inhibited by tetrodotoxin and therefore was independent of cellular electrical activity, the G protein inhibitor pertussis toxin prevented stretch‐induced cyclooxygenase activation. Pertussis toxin also inhibited stretch‐induced increases in PGF_2α production, phospholipase D activation, and cell growth. It is concluded that stretch of skeletal muscle increases muscle cell growth through a G protein‐dependent process involving the activation of cyclooxygenase, an immediate early gene product.