Modulation of the Rat Hippocampal Dinucleotide Receptor by Adenosine Receptor Activation

Abstract

Diadenosine pentaphosphate (Ap(5)A) and ATP stimulate an intracellular free calcium concentration ([Ca(2+)](I)) increase in rat hippocampal synaptosomes via different receptors as demonstrated by the lack of cross-desensitization between Ap(5)A and ATP responses. The ATP response was inhibited by P2 receptor antagonists and not by the dinucleotide receptor antagonist, diinosine pentaphosphate (Ip(5)I). In contrast, the Ap(5)A response was inhibited by Ip(5)I but not by P2 receptor antagonists. Studies in single hippocampal synaptic terminals showed that 31% of them responded to Ap(5)A by a [Ca(2+)](i) increase. Adenosine receptors (A(1), A(2A), and A(3)) were also present in isolated terminals as demonstrated by immunohistochemistry. The activation of A(1) or A(2A) receptors by specific agonists changed the sigmoid concentration-response curve for Ap(5)A (EC(50) = 33.5 +/- 4.5 microM) into biphasic curves. When the high-affinity adenosine receptors A(1) or A(2A) were activated, the Ap(5)A dose-response curves showed a high-affinity component with EC(50) values of 41.1 +/- 1.9 pM and 99.9 +/- 10.2 nM, respectively. The low-affinity component showed EC(50) values of 17.1 +/- 0.8 and 21.6 +/- 1.4 microM for A(1) and A(2A) receptor activation, respectively. However, the adenosine A(3) receptor activation induced a right shift of the dinucleotide concentration-response curve, showing an EC(50) value of 331.4 +/- 54.6 microM. In addition, in the presence of the A(2A) agonist, the Ap(5)A calcium influx responses were increased up to 300% of the control values. These results clearly demonstrate that the activation of presynaptic adenosine receptors is able to modulate the dinucleotide response in hippocampal nerve terminals.

Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen–glucose deprivation episodes of different duration

“…Of the four adenosine receptor subtypes, the adenosine A 3 receptor is the most recently cloned [2]. A 3 receptors have a widespread distribution in the rat brain [3] and in the hippocampus are preferentially expressed on nerve terminals [4,5]. The expression of A 3 receptors in the brain is lower than that of other adenosine receptor subtypes [6], and the affinity for adenosine, calculated from binding experiments in rat brain membranes (6.5 μM [2]), is lower than that of A 1 [7] and A 2A [8] receptors.…”

Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological Analysis

“…For immunochemical analysis, synaptosomes from striata of male Wistar rats (6 weeks old) and male CD-1 mice (see above) were obtained through a discontinuous Percoll gradient, following the procedure described by Díaz-Hernandez et al (2002), with minor modifications. Striata were homogenized in 0.25 M sucrose and 5 mM N-[tris [hydroxymethyl]methyl]-2-aminoethanesulfonic acid (TES), pH 7.4.…”

Diadenosine Polyphosphate Analog Controls Postsynaptic Excitation in CA3-CA1 Synapses via a Nitric Oxide-Dependent Mechanism

“…For instance, AppCH 2 ppA may be acting through control of the ectoprotein kinase (Ehrlich et al, 1986;Chen et al, 1996). Another mechanism could be the modulation of hippocampal dinucleotide receptors by activation of adenosine receptors, as recently demonstrated in the rat hippocampal synaptosomes (Diaz-Hernandez et al, 2002). Such modulation, demonstrated for diadenosine polyphosphate and adenosine receptors, could reinforce effects of AppCH 2 ppA operating through our suggested pathway.…”