CATABOLISM OF AP(4)A AND AP(5)A BY RAT-BRAIN SYNAPTOSOMES

Adenosine 5',5'''-P-1,P-4-tetraphosphate (Ap(4)A) and adenosine 5',5'' '-P-1,P-5-pentaphosphate (Ap(5)A) are stored in and released from rat brain synaptic terminals. In the present study we investigated the hyd rolysis of dinucleotides (Ap(4)A and Ap,A) in synaptosomes from the ce rebral colter of adult rats. Ap,A and Ap,A, but not Ap,A, were hydroly zed at pH 7.5 in the presence of 20 mM Tris/HCl, 2.0 mM MgCl2, 10 mM g lucose and 225 mM sucrose at 37 degrees C. The disappearance of the su bstrates measured by FPLC on a mono-Q HR column was both time and prot ein dependent. Since synaptosome integrity was at least 90% at the end of the assay, hydrolysis probably occurred by the action of an ecto-e nzyme. Extracellular actions of adenine dinucleotides at central nervo us system terminate due to the existence of ecto-nucleotidases which s pecifically cleave these dinucleotides. These enzymes in association w ith an ATP diphosphohydrolase and a 5'-nucleotidase are able to promot e the complete hydrolysis of dinucleotides to adenosine in the synapti c cleft.