Cycloheximide: an adrenergic agent.
Cycloheximide, a widely used inhibitor of protein synthesis, stimulates glycogenolysis, gluconeogenesis and ureogenesis in isolated rat hepatocytes. The effects of cycloheximide were compared to those of norepinephrine. Both agents, cycloheximide and norepinephrine, produced slight increases in the levels of cyclic AMP (30% increases) which were blocked by propranolol. Interestingly, it was found that the metabolic actions of norepinephrine and cycloheximide (stimulation of glycogenolysis, gluconeogenesis and ureogenesis) were only slightly diminished by the beta adrenergic antagonist propranolol but abolished by the selective alpha 1 adrenergic antagonist prazosin. The ability of cycloheximide to inhibit protein synthesis was not affected by either prazosin or propranolol. It is concluded that the stimulation of glycogenolysis, gluconeogenesis and ureogenesis by cycloheximide in rat hepatocytes, is an effect of the antibiotic independent of its ability to inhibit protein synthesis and that is mediated through activation of alpha 1 adrenoceptors. The adrenergic activity of cycloheximide should be considered when this drug is used as an inhibitor of protein synthesis.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D009638:Norepinephrine; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D008112:Liver Glycogen; D011943:Receptors, Adrenergic, beta; D003513:Cycloheximide; D011433:Propranolol; D000242:Cyclic AMP; D009638:Norepinephrine; D011224:Prazosin