Adenosine triphosphate and diadenosine pentaphosphate induce [Ca²⁺]_i increase in rat basal ganglia aminergic terminals

Abstract

Synaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap(5)A, which stimulate a [Ca(2+)](i) increase in the presynaptic terminals via specific ionotropic receptors, termed P2X, and diadenosine polyphosphate receptors. Aminergic terminals from rat brain basal ganglia were characterized by immunocolocalization of synaptophysin and the vesicular monoamine transporter VMAT2 and represent 29% of the total. These aminergic terminals respond to ATP and/or Ap(5)A with an increase in the intrasynaptosomal calcium concentration as measured by a microfluorimetric technique. This technique, which allows single synaptic terminals to be studied, showed that roughly 8.2% +/- 1.6% of the aminergic terminals respond to ATP, 16.9% +/- 1.3% respond to Ap(5)A, 32.6% +/- 0.8% to both, and 42.3% +/- 1.5% of them have no response. Immunological studies performed with antibodies against ionotropic ATP receptor subunits showed positive labelling with anti-P2X(3) antibodies in 39% of the terminals. However, colocalization studies of VMAT and P2X(3) receptor subunit indicate that only 25% of the aminergic terminals also contain this receptor subtype. These results demonstrate that the aminergic terminals from the rat brain basal ganglia are to a large extent under the modulation of presynaptic nucleotide and dinucleotide receptors.

Dinucleoside polyphosphates and their interaction with other nucleotide signaling pathways

“…We explored the interaction between dinucleotide receptor activation and the exocytotic release of other neurotransmitters. Using microfluorimetric Ca 2+ measurement techniques combined with immunocytochemical studies, we showed the presence of the dinucleotide receptor in aminergic terminals isolated from basal ganglia [23]. A specific receptor for diadenosine polyphosphates is also present in cholinergic terminals from rat midbrain as well as in GABAergic or glutamatergic terminals obtained from the same source.…”

Cystathionine β-Synthase (CBS) Domain-containing Pyrophosphatase as a Target for Diadenosine Polyphosphates in Bacteria

“…Ap n As are involved in many other processes, including neurotransmission (15), apoptosis (16), and analgesia (17). Of note, Ap 4 A is used in hypoxia therapy in humans (18).…”

Reduced Energy Utilization in the Brain is a Feature of an Animal Model of Fatigue

“…These results suggest that, under the condition of fatigue, serotonergic and dopaminergic turnover in the synaptic terminals is not properly activated, and thus fatigue sensation and physical activity are insufficient. Because maintenance of synaptic transmission requires energy (Atwood et al, 1972;Nguyen et al, 1997), and stimulation of synaptic release and recycling of synaptic vesicles is induced through ATP receptors in the presynaptic aminergic terminals (Giraldez et al, 2001), insufficient serotonin and dopamine turnover in the synaptic terminals might occur due to reduced energy utilization in the brain of the rest-deprived, fatigued rats.…”