Adenosine 5'-monophosphate transport across the membrane of synaptosomes and myelin.
Synaptosome-enriched preparations from rat and guinea pig brain tissue vigorously accumulated [3H]-adenosine 5'-monophosphate ([3H]AMP). When the accumulation of [3H]AMP was determined using incubation periods of 30 s or less, high concentrations of adenosine, dipyridamole and soluflazine did not inhibit the accumulation of label appreciably. The accumulation of [3H]AMP was saturable, temperature-dependent, osmotic-sensitive and exhibited structural specificity. Based on the kinetics of uptake by different subcellular fractions, and the inhibitory effects of other nucleotides, the uptake of AMP appeared to be mediated by three saturable systems with Kt values of approximately 0.2, 6, and 100 microM. The transport system with the highest affinity for AMP was selectively inhibited by guanosine 5'-monophosphate, and its Vmax was several fold higher in a myelin-enriched fraction than in synaptosome-enriched fractions. The transport system with the Kt approximately 6 microM was selectively inhibited by alpha, beta-methylene adenosine diphosphate, and its Vmax was several times higher in a fraction enriched in high-density synaptosomes than in fractions enriched in low-density synaptosomes or myelin. Both of these transport systems were potently inhibited by ATP and ADP. Nucleotides that were either weak or inactive as inhibitors of AMP transport included 3'-AMP, cyclic AMP, guanosine 5'-diphosphate, and the 5'-mononucleotides of cytosine, inosine, and uridine. GTP consistently enhanced uptake at concentrations greater than or equal to 1 microM. The transport of AMP was not Na(+)-dependent and was not inhibited by membrane depolarization. This transport system may mediate the release of AMP for subsequent conversion to adenosine extracellularly.
Shank
R P
RP
Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477-0776.
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D005260:Female; D006157:Guanosine Monophosphate / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials; D009186:Myelin Sheath / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D013570:Synaptic Membranes / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D013696:Temperature
C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D006157:Guanosine Monophosphate; D000255:Adenosine Triphosphate