Ribavirin administration alters ectonucleotidase activities in experimental autoimmune encephalomyelitis.
The role of extracellular purines and purinoreceptors in the pathophysiology of different neurological disorders is the focus of rapidly expanding area of research. Ectonucleotidases are the enzymes with multiple roles in extracellular nucleotides metabolism and regulation of nucleotidebased intercellular signaling. The aim of present study was to investigate the changes in the ATP, ADP and AMP hydrolyzing activities after ribavirin treatment in spinal cord during experimental autoimmune encephalomyelitis (EAE). Our results demonstrate that ribavirin itself had no significant effect on ectoenzyme activities, when tested in vitro and in vivo on spinal cord crude membrane preparation of intact animals. We observed significant increase in ATP, ADP and AMP hydrolyzing activity in the spinal cord crude membrane preparation in EAE animals at 15 days post immunization compared to control animals. The increase was registered at 28 days post immunization, as well. At same time points, ribavirin treatment decreased ATP, ADP and AMP hydrolyzing activity compared to EAE animals. In addition, no significant changes 8 days post immunization was observed between EAE-induced and ribavirin- treated EAE animals and these levels were similar to control level. Thus, we suppose that ribavirin-induced alteration in ectonucleotidase activities is rather due to its suppression of inflammation, than to its direct action on ATP, ADP and AMP hydrolysis.
Lavrnja
Irena
I
Department of Neurobiology, Institute for Biological Research Sinisa Stanković, Bulevar Despota Stefana 142, Belgrade, Serbia. irenam@ibiss.bg.ac.rs
Nedeljkovic
Nadezda
N
Bjelobaba
Ivana
I
Stojkov
Danijela
D
Dacic
Sanja
S
Pekovic
Sanja
S
Rakic
Ljubisav
L
Mostarica-Stojkovic
Marija
M
Stosic-Grujicic
Stanislava
S
Stojiljkovic
Mirjana
M
D015720:5'-Nucleotidase / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006868:Hydrolysis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D012254:Ribavirin / Q000008:administration & dosage* / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D000227:Adenine Nucleotides; D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D012254:Ribavirin; D015720:5'-Nucleotidase; D000241:Adenosine