Presynaptic signalling mediated by mono- and dinucleotides in the central nervous system

Synaptosomal preparations from rat midbrain exhibit specific responses to b oth ATP and Ap(5)A, which elicit a Ca2+ entrance to the presynaptic termina ls. 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 mon onucleotide ATP. At the presynaptic level: diinosine pentaphosphate, Ip(5)I , is a good tool to specifically block dinucleotide responses, which are in hibited at low nM concentration, versus the high mu M concentrations requir ed to block ATP responses. There is evidence for a presynaptic control of m ononucleotide and dinucleotide responses, mediated by metabotropic and iono tropic receptors. Stimulation of adenosine A1 receptors increases the affin ity of dinucleotide receptors by five orders of magnitude, from 30 mu M to 680 pM for control and in the presence of A1 agonist, respectively. (C) 200 0 Elsevier Science B.V. All rights reserved.