Presynaptic signalling mediated by mono- and dinucleotides in the central nervous system.
Synaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap(5)A, which elicit a Ca(2+) entrance to the presynaptic terminals. Studies of isolated single terminals showed that not all the terminals contain ionotropic receptors for nucleotides, in fact only 46% of them do. Of these, 12% responded only to the dinucleotide Ap(5)A, and 20% to the mononucleotide ATP. At the presynaptic level, diinosine pentaphosphate, Ip(5)I, is a good tool to specifically block dinucleotide responses, which are inhibited at low nM concentration, versus the high microM concentrations required to block ATP responses. There is evidence for a presynaptic control of mononucleotide and dinucleotide responses, mediated by metabotropic and ionotropic receptors. Stimulation of adenosine A1 receptors increases the affinity of dinucleotide receptors by five orders of magnitude, from 30 microM to 680 pM for control and in the presence of A1 agonist, respectively.
Miras-Portugal
M T
MT
Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040, Madrid, Spain. mtmiras@eucmax.sim.ucm.es
Díaz-Hernández
M
M
Gomez-Villafuerte
R
R
Gualix
J
J
Castro
E
E
Pintor
J
J
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009711:Nucleotides / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D009711:Nucleotides; D017661:Receptors, Presynaptic