Mechanical stimulation of skeletal muscle increases prostaglandin F2 alpha production, cyclooxygenase activity, and cell growth by a pertussis toxin sensitive mechanism.
Repetitive mechanical stimulation of differentiated skeletal muscle in tissue culture increased the long-term production of prostaglandin F2 alpha, 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 Km, with little change in its Vmax. 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 PGF2 alpha 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.
Vandenburgh
H H
HH
Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, Rhode Island 02906, USA.
Shansky
J
J
Solerssi
R
R
Chromiak
J
J
D000818:Animals; D001717:Birds; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015237:Dinoprost / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000196:embryology*; D037342:Pertussis Toxin; D010812:Physical Stimulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007527:Isoenzymes; D010566:Virulence Factors, Bordetella; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D037342:Pertussis Toxin