title: Binding of 5'-O-(2-thiodiphosphate) to rat brain membranes is prevented by diadenosine tetraphosphate and correlates with ecto-nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) activity.
abstract: The distribution of binding sites for [(35)S]5'-O-(2-thiodiphosphate) ([(35)S]ADPbetaS), a radioligand of P2Y(1,12,13) receptors, and of ecto-nucleotide pyrophosphatase phosphodiesterase activity were analyzed in the rat forebrain. Binding sites for the radilogand are widespreadly distributed in the rat forebrain, showing the highest density in hypothalamus. K(d) values were in the range 1-2 nM. Diadenosine tetraphosphate (Ap(4)A) and diethenoadenosine tetraphosphate, epsilon-(Ap(4)A), displaced the radioligand, indicating dinucleotide binding to ADPbetaS-recognizing P2Y receptors. Activity ecto-nucleotide pyrophosphatase phosphodiesterase 1 (NPP1), able to hydrolyze Ap(4)A and other diadenosine polyphosphates, is also widely distributed through the rat forebrain, with the highest activity in hypothalamus. These results suggests that Ap(4)A signalling mediated by P2Y(1,12,13) receptors and enzymatically regulated by NPP1 activity may be particularly important in hypothalamus and add new support for neurotransmitter/neuromodulatory functions of diadenosine polyphosphates in brain.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of La Laguna, 38206 La Laguna, Tenerife, Spain.
authors.forename: Sol
authors.initials: S
authors.lastname: Oaknin
authors.forename: Carmen Rosa
authors.initials: CR
authors.lastname: Rodríguez-Ferrer
authors.forename: Antonio
authors.initials: A
authors.lastname: Ramos
authors.forename: José Santiago
authors.initials: JS
authors.lastname: Aguilar
authors.forename: Pedro
authors.initials: P
authors.lastname: Rotllán
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D005625:Frontal Lobe / Q000201:enzymology; D007031:Hypothalamus / Q000201:enzymology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013462:Sulfur Radioisotopes; D013702:Temporal Lobe / Q000201:enzymology; D013873:Thionucleotides / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018377:Neurotransmitter Agents; D018048:Receptors, Purinergic P2; D013462:Sulfur Radioisotopes; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D000244:Adenosine Diphosphate; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D017766:Acid Anhydride Hydrolases; D011755:Pyrophosphatases; C020023:bis(5'-nucleosyl)tetraphosphatase (asymmetrical)