title: Receptor binding properties of di (1,N6-ethenoadenosine) 5', 5'''-P1, P4-tetraphosphate and its modulatory effect on extracellular glutamate levels in rat striatum.
abstract: Our aim was to investigate the neuromodulatory role of diadenosine tetraphosphate (Ap(4)A). Ap(4)A-binding sites were detected in striatum and hippocampus membranes using [(35)S]-ADP beta S as radioligand and Ap(4)A and epsilon-(Ap(4)A), di-ethenoadenosine tetraphosphate, as displacers. Effects of epsilon-(Ap(4)A) on extracellular glutamate levels were studied using intracerebral perfusion. Both areas contain high-affinity binding sites for [(35)S]-ADP beta S with K(d) values in the low nM range. [(35)S]-ADP beta S binding was displaced by Ap(4)A and epsilon-(Ap(4)A). At 1 and 10 microM doses, epsilon-(Ap(4)A) markedly decreased glutamate levels in the striatum. The possibility of Ap(4)A acting as an endogenous modulator of excitatory neurotransmission is discussed.
authors.affiliation: Department of Biochemistry and Molecular Biology. Faculty of Biology, University of La Laguna, 38206 La Laguna, Tenerife, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Oaknin
authors.forename: C R
authors.initials: CR
authors.lastname: Rodríguez-Ferrer
authors.forename: J S
authors.initials: JS
authors.lastname: Aguilar
authors.forename: A
authors.initials: A
authors.lastname: Ramos
authors.forename: P
authors.initials: P
authors.lastname: Rotllán
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013873:Thionucleotides / Q000378:metabolism
chemical_list: D015226:Dinucleoside Phosphates; D018377:Neurotransmitter Agents; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D018698:Glutamic Acid; C020733:diadenosine tetraphosphate; D000244:Adenosine Diphosphate; C068203:di(1,N(6)-ethenoadenosine)-5',5'''-P(1),P(4)-tetraphosphate