MECHANICAL STIMULATION OF SKELETAL-MUSCLE CELLS MITIGATES GLUCOCORTICOID-INDUCED DECREASES IN PROSTAGLANDIN PRODUCTION AND PROSTAGLANDIN SYNTHASE ACTIVITY

The glucocorticoid dexamethasone (Dex) induces a decline in protein sy nthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch . Since the prostaglandin synthesis inhibitor indomethacin mitigated t his stretch attenuation of muscle atrophy, the effects of Dex and mech anical stretch on prostaglandin production and prostaglandin H synthas e (PGHS) activity were examined. In static cultures, 10(-8) M Dex redu ced PGF(2 alpha) production 55-65% and PGE(2) production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-t reated cultures increased PCF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE(2) production 51% at 24 h and 236% at 72 h. Mech anical stimulation of Dex-treated cultures increased PGF(2 alpha) prod uction 162% after 24 h, returning PGF(2 alpha), efflux to the revel of non-Dex-treated cultures. At 72 h, stretch increased PGF(2 alpha) eff lux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE(2) production at 24 h, but not at 72 h. D ex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures in creased PGHS activity by 98% after 24 h. Repetitive mechanical stimula tion attenuates the catabolic effects of Dex on cultured skeletal musc le cells in part by mitigating the Dex-induced declines in PGHS activi ty and prostaglandin production. (C) 1994 Wiley-Liss, Inc.