Presynaptic Adenosine and P2Y Receptors

Abstract

Adenine-based purines, such as adenosine and ATP, are ubiquitous molecules that, in addition to their roles in metabolism, act as modulators of neurotransmitter release through activation of presynaptic P1 purinoceptors or adenosine receptors (activated by adenosine) and P2 receptors (activated by nucleotides). Of the latter, the P2Y receptors are G protein-coupled, whereas the P2X receptors are ligand-gated ion channels and not covered in this review.

Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons

“…ATP is involved in a number of physiological functions, such as neuroprotection, locomotion, development, and pain, through the activation of multiple types of P2 receptors (e.g., ionotropic P2X and metabotropic P2Y receptors) expressed on neuronal membranes (Ralevic and Burnstock, 1998;Burnstock, 2007). P2 receptors are also expressed on presynaptic nerve terminals, and regulate the release of a variety of neurotransmitters (Rodrigues et al, 2005;Dorostkar and Boehm, 2008;Gonçalves and Queiroz, 2008). Moreover, extracellular ATP can be rapidly hydrolyzed to ADP, AMP, and adenosine via multiple types of extracellular Abbreviations: ab-me-ATP, ab-methylene-ATP; APV, DL-2-amino-5-phosphonovaleric acid; ARL67156, 6-N,N-diethyl-b-g-dibromomethylene-D-adenosine-5 0 -triphosphate; BBG, Brilliant Blue G; Bz-ATP, 2 0 -3 0 -O-(4-benzoylbenzoyl)-ATP; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; DRG, dorsal root ganglia; ENT1, equilibrative nucleoside transporter 1; EPSCs, excitatory postsynaptic currents; KeS test, KolmogoroveSmirnov test; mEPSCs, miniature EPSCs; MRS2179, 2'-deoxy-N 6 -methyl adenosine 3 0 ,5'-diphosphate; MRS2211, 2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-2-[(2-chloro-5-nitrophenyl)azo]-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde; MRS2395, propionyloxymethyl)-propyl ester; NBMPR, S-(4-nitrobenzyl)-6-thioinosine; NT5E, ecto-5'-nucleotidases; NTPDases, ecto-nucleoside triphosphate diphosphohydrolases; PAP, prostatic acid phosphatase; PPADS, pyridoxalphosphate-6-azophenyl-2 0 ,4'-disulfonic acid; PPR, pairedpulse ratio; SR95531, 6-imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid; TG, trigeminal ganglia; TNAP, tissue nonspecific alkaline phosphatase; TTX, tetrodotoxin; VDCCs, voltage-dependent Ca 2þ channels.…”

P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb

“…P2X receptors are involved in fast synaptic transmission, e.g., in the medial habenula, the hippocampus, and the cerebral cortex [7][8][9]. P1 and P2Y receptors mediate synaptic plasticity by interaction with ion channels and receptors in many (if not all) brain regions such as the hippocampus, the cerebellum, the striatum and cerebral cortex [10][11][12]. In the mouse olfactory bulb, evidence for functional expression of purinoceptors was published only recently (reviewed in [13]).…”

Facilitation of transmitter release from rat sympathetic neurons via presynaptic P2Y1 receptors

“…However, evidence for presynaptic P2Y1 receptors is scarce and, if available, only favours inhibitory presynaptic P2Y1 receptors, as suggested for peripheral sensory neurons (Gerevich et al, 2004), for hippocampal neurons (Rodrigues et al, 2005;Csolle et al, 2008), for spinal cord neurons and also for sympathetic neurons (Quintas et al, 2009). In general, presynaptic P2Y receptors have been shown to mediate inhibition, but not facilitation, of transmitter release (Goncalves and Queiroz, 2008). Hence, the results of this study provide the first evidence for an …”

“…Amongst the members of the adrenoceptor family, presynaptic a2A and a2C receptors mediate autoinhibition of noradrenaline release, whereas b2 receptors mediate facilitation . Within the family of P2 receptors, ionotropic P2X receptors mediate facilitation of transmitter release, whereas metabotropic P2Y receptors were found to mediate inhibition only (Sperlagh et al, 2007;Dorostkar and Boehm, 2008;Goncalves and Queiroz, 2008). In this respect, the family of P2Y receptors appear to differ from other GPCRs: most neurotransmitters and/or mediators, such as acetylcholine, adenosine, histamine, noradrenaline and prostaglandins are known to cause presynaptic inhibition as well as facilitation of sympathetic transmitter release, the two opposing actions being mediated by two different GPCRs .…”

“…However, with respect to the sub-classification of presynaptic P2Y receptors, the information available is limited, as most subtype selective ligands have been developed quite recently (Jacobson and Boeynaems, 2010). In fact, P2Y1, P2Y2, P2Y4, P2Y12 and P2Y13 receptors have all been implicated in the presynaptic inhibition of transmitter release, but unequivocal evidence for facilitatory presynaptic P2Y receptors is lacking (Goncalves and Queiroz, 2008).…”