Heparin modulates adenine nucleotide hydrolysis by synaptosomes from cerebral cortex.
The modulatory effect of heparin and dextran sulfate 500,000 (sulfated polysaccharides) was studied on ATPDase and 5'-nucleotidase activities. These enzymes participate in the degradation of ATP and adenosine production at the synaptic cleft level. Nucleotide hydrolysis was inhibited by heparin and dextran sulfate 500,000. For ADP, the inhibition was more evident at low cation concentrations (0.15 mM Ca2+ or Mg2+), reaching a maximum of 75%. For ATP, the inhibitory effect was less prominent and independent of divalent cation concentration, reaching a maximum of 25%. For AMP, the inhibition observed was similar with either relatively high (1 mM) or with low Mg2+ concentrations tested (0.1 mM) and reached a maximum of 35%. K+ did not change the inhibitory potency of sulfated polysaccharide suggesting that its effects were not exclusively related to charge interaction. These results suggest that heparin and possibly other naturally occurring sulfated polysaccharides may have a potential role as modulator of extracellular nucleotide hydrolysis in the synaptic cleft region.
Department of Chemistry, Natural and Exact Sciences Center, Federal University of Santa Maria, RS, Brazil. mrosa@base.ufsm.br
M R
MR
Schetinger
F
F
Falquembach
F
F
Michelot
A
A
Mezzomo
J B
JB
Rocha
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000648:ultrastructure*; D016264:Dextran Sulfate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006868:Hydrolysis; D008274:Magnesium / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology*
D000227:Adenine Nucleotides; D004791:Enzyme Inhibitors; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D006493:Heparin; D016264:Dextran Sulfate; D015720:5'-Nucleotidase; D001081:Apyrase; D008274:Magnesium; D002118:Calcium