Protein synthesis inhibition by cycloheximide does not affect the acute release of tissue-type plasminogen activator

The acute release of tissue-type plasminogen activator (t-PA) was studied in perfused rat hindlegs. Pretreatment of rats with the protein syNthesis inhibitor cycloheximide (2 mg/kg) at 1, 3 or 5 h prior to perfusion of rat hindlegs did not influence the amount of t-PA released by platelet-activating factor (20 nM) or bradykinin (1 microM). The amount of t-PA activity that could be extracted from hindleg skeletal muscle was not decreased by cycloheximide pretreatment though it was decreased in lung extracts. The in vivo release of t-PA was not affected by cycloheximide pretreatment. The data suggest that the acute release of t-PA from vascular endothelial cells does not require ongoing protein synthesis, but that acutely released t-PA is derived from a stable endothelial storage pool.