Inhibition of glycosylation by corynetoxin, the causative agent of annual ryegrass toxicity: a comparison with tunicamycin.
The biological activities of corynetoxins, the causative agents of annual ryegrass toxicity, were compared with those of the closely related tunicamycins and found to be essentially identical. Both showed similar antibiotic activity against Newcastle disease virus and a range of gram-positive bacteria. In preparations of rat liver rough microsomes they also strongly inhibited the uridine diphospho-N-acetylglucosamine (UDP-GlcNAc):dolichol-P N-acetylglucosamine-1-phosphate (GlcNAc-1-P) transferase, an enzyme essential for N-glycosylation of glycoproteins. Pretreatment of rats with corynetoxins resulted in dose- and time-related reduction in the level of activity of this transferase in liver microsomal preparations. The implications of this reduction are discussed with reference to annual ryegrass toxicity, the only field disease known to be caused by tunicamycin-related compounds. Both corynetoxin and tunicamycin produced similar neurological effects and increased vascular permeability in nursling rats and they showed similar LD50-values of 137 and 132 micrograms/kg, respectively, in the nursling rats.
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D050260:Carbohydrate Metabolism; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006017:Glycolipids / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D051381:Rats; D017855:Transferases (Other Substituted Phosphate Groups); D014415:Tunicamycin / Q000494:pharmacology*
D006017:Glycolipids; C034696:corynetoxins; D014415:Tunicamycin; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C023222:UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase; D005952:Glucose-6-Phosphatase; D005944:Glucosamine