Ecto-nucleotidase of cultured rat superior cervical ganglia: dipyridamole is a novel inhibitor.
Based on studies of agonist potencies on intact rat superior cervical ganglia, it has been suggested that this ganglion possesses distinct receptors for purine and pyrimidine nucleotides. However, the potency of an agonist is dependent upon whether it is susceptible to extracellular metabolism by the tissue. The aim of this investigation was to study the metabolism of uridine or adenosine nucleotides and nucleosides and the effects of dipyridamole and an ecto-ATPase inhibitor ARL 67156 (6-N, N-diethyl-D-beta-gamma-dibromomethylene-ATP) on their metabolism. Adenosine- and uridine-5'-triphosphates (ATP and UTP) were catabolised by cultured rat superior cervical ganglia, to their di- and monophosphates. Both ATP and UTP breakdown was significantly inhibited by dipyridamole (10 mcM), whereas ARL 67156 (100 mcM), was a weaker inhibitor of ATP degradation and inhibited UTP breakdown by approximately 40%. Metabolism of ATP and UTP by cultured rat superior cervical ganglia was reduced after treatment with cytosine-beta-arabinoside, suggesting that non-neuronal cells along with neuronal cells contribute to their breakdown. In conclusion, these results indicate that rat superior cervical ganglia possess ecto-nucleotidases capable of catabolising purine and pyrimidine nucleotides to their nucleosides, and that dipyridamole is a potent inhibitor of ecto-nucleotidase activity.
Connolly
G P
GP
Purine NeuroScience Laboratory, Department of Chemical Pathology, Guy's, King's and St. Thomas' Medical Schools, 5th Floor Guy's Tower, London Bridge, SE1 9RT, London, UK. gerald.connolly@kcl.ac.uk
Duley
J A
JA
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D008954:Models, Biological; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors; D014544:Uridine Triphosphate / Q000378:metabolism
D018722:Nicotinic Agonists; D003561:Cytarabine; D004246:Dimethylphenylpiperazinium Iodide; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D014544:Uridine Triphosphate