Glycyl-L-glutamine, a precursor, and glycyl-L-glutamic acid, a neurotrophic factor for maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat in vivo.
L. W. Haynes and M. E. Smith have reported [(1985) Biochem. Soc. Trans. 13, 174-175] that glycyl-L-glutamine (Gly-Gln) increases the A12 and G4 forms of acetylcholinesterase (AcChoEase) in cultured embryonic rat skeletal muscle. Since Gly-Gln meets the criteria established for the neurotrophic factor (NF) in extracts of central nervous system/sciatic nerves that maintains AcChoEase and butyrylcholinesterase (BtChoEase) in the denervated cat superior cervical ganglion (SCG) in vivo, it was tested by the latter procedure. Solutions of Gly-Gln (10(-7)-10(-3) M) in 0.9% NaCl solution were infused for 24 hr via the right common carotid artery of cats with preganglionically denervated SCG, following ligation of the external carotid and lingual arteries. At 48 hr postdenervation, the AcChoEase and BtChoEase contents of the right SCG were within the range of similarly treated controls infused with 0.9% NaCl solution; the AcChoEase and BtChoEase contents of the left SCG, where the infused solutions arrived by way of a much more circuitous route, were significantly elevated at concentrations of Gly-Gln of 10(-5) M and higher. This suggested that the neurotrophic effect on the left SCG was produced by a metabolite of Gly-Gln. Accordingly, glycine, L-glutamine, and glycyl-L-glutamic acid (Gly-Glu) were then tested. Glycine and L-glutamine were inactive; Gly-Glu, 10(-6)-10(-5) M, exerted a significantly positive neurotrophic effect at both the right and left SCG; at 10(-4) M, the effect was absent. The method employed currently for preparation of extracts of SCG for assay of AcChoEase, BtChoEase, and protein contents (homogenization of scissor-minced ganglia in water) was compared with homogenization in molar NaCl/1% Triton X-100. Values obtained by the former procedure, in comparison with the latter, were 91% +/- 7% for AcChoEase and 83% +/- 7% for BtChoEase, expressed as substrate hydrolyzed per mg of protein per min.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002415:Cats; D002802:Cholinesterases / Q000378:metabolism*; D003714:Denervation; D004151:Dipeptides / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000378:metabolism*
D004151:Dipeptides; C039788:glycylglutamine; C046223:N-glycylglutamic acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases