title: Glucosaminylmuramyl dipeptide-induced changes in murine macrophage metabolism.
abstract: The purpose of the study was to investigate influence of glucosaminyl muramyl dipeptide (GMDP) and its derivatives on adenosine deaminase (ADA, CE 3.5.4.4.) and 5'-nucleotidase (5-N, CE 3.1.3.5) activity in murine macrophages in vitro. The intensity of superoxide radicals (O2-) formation by these cells has been also studied. GMDP incubated with macrophages was found to inhibit substantially the activity of 5-N, without affecting the activity of ADA in these cells. The maximal effect on 5-N activity was noted following 24 h of co-culture and was accompanied by a higher intensity of O2- formation. GMDP added in doses ranging from 0.01 to 1 microgram/ml induced a gradual decrease in 5-N activity, with an increase in activity of the O2- -generating system. The GMDP analog with double dipeptide link GM(DP)2 has demonstrated the same activating effect as GMDP. The presence of dipeptide alanyl-D-isoglutamine in the GMDP structure is necessary for realization of the drug activating effect, as N-acetylglucosaminyl-N-acetylmuramyl failed to influence macrophage activity. Neither D-D nor L-L isomers of the drug affect the 5-N activity and O2- formation in macrophages. The mechanism of macrophages activation induced by GMDP may include the inhibition of 5-N activity and the stimulation in production of superoxide radicals.
authors.affiliation: Kavetsky Institute for Oncology Problems, Kiev, AS UkrS.S.R.
authors.forename: K P
authors.initials: KP
authors.lastname: Balitsky
authors.forename: V Y
authors.initials: VY
authors.lastname: Umansky
authors.forename: A M
authors.initials: AM
authors.lastname: Tarakhovsky
authors.forename: T M
authors.initials: TM
authors.lastname: Andronova
authors.forename: V T
authors.initials: VT
authors.lastname: Ivanov
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology / Q000031:analogs & derivatives; D000243:Adenosine Deaminase / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity; D013481:Superoxides / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D013481:Superoxides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C023868:N-acetyl-beta-glucosaminyl-N-acetylmuramyl-alanylisoglutamine; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase