Dual Presynaptic Control by ATP of Glutamate Release via Facilitatory P2X1, P2X2/3, and P2X3and Inhibitory P2Y1, P2Y2, and/or P2Y4Receptors in the Rat Hippocampus

Rodrigues, Ricardo J.; Almeida, Teresa; Richardson, Peter J.; Oliveira, Catarina R.; Cunha, Rodrigo A.

doi:10.1523/jneurosci.0628-05.2005

Cited by 202 publications

(183 citation statements)

References 49 publications

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“…Increase in extracellular ADP and AMP concentrations observed in the present study can be beneficial for the hippocampus by inhibiting deleterious glutamate neurotransmittermediated effects [27][28][29] and microglial cytokine actions [30,31]. Recent evidence indicates that AMP also activates A1 receptors and when tested in a model of kainate-induced Values are means ± SE Student's t test, **p < 0.007; *p < 0.03 seizure, AMP prolonged latency of convulsions, but had no effects on seizure severity and mortality.…”

Section: Discussionmentioning

confidence: 73%

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

Doná

Conceição

Ulrich

et al. 2016

Purinergic Signalling

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Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

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Section: Discussionmentioning

confidence: 73%

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

Doná

Conceição

Ulrich

et al. 2016

Purinergic Signalling

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“…Nerve terminals from the rat hippocampus were purified through sucrose and Percoll gradients (Rebola et al, 2005;Rodrigues et al, 2005a). We have already validated the use of these hippocampal synaptosomes to study age-related modifications of biochemical and functional properties of nerve terminals (Cunha et al, 2001;Lopes et al, 1999;Rebola et al, 2003a;Rodrigues et al, in press).…”

Section: Preparation Of Hippocampal Nerve Terminalsmentioning

confidence: 99%

“…After blocking for 2 h at room temperature with 5% milk in Tris-buffered saline, pH 7.6 containing 0.1% Tween 20 (TBS-T), the membranes were incubated overnight at 4 • C with the different antibodies, namely: widely used mouse anti-␣-tubulin (1:10,000 dilution, from Sigma-Portugal) and goat anti-glyceraldeheyde-3-phosphate dehydrogenase (GAPDH, 1:1000 dilution, from Santa Cruz Biotechnology, Alfagene, Portugal); previously validated (see Pinheiro et al, 2003) mouse anti-synaptophysin (1:1000, from Sigma) and mouse anti-SNAP-25 (1:10,000, from Sigma); previously used (e.g. Köfalvi et al, 2005) guinea-pig anti-vesicular GABA transporter (vGAT, 1:1000, from Calbiochem, PGHitec, Portugal), guinea-pig anti-vesicular glutamate transporters types 1 and 2 (vGluT1 and vGluT2, 1:5000, from Chemicon) and guinea-pig anti-vesicular acetylcholine transporter (vAChT, 1:500, from Chemicon); previously validated rabbit anti-adenosine A 1 receptor (1:1000, from Affinity Bioreagents, Golden, USA; see Rebola et al, 2003b), goat anti-adenosine A 2A receptor (1:500 dilution, from Santa Cruz Biotechnology; see Rebola et al, 2005), rabbit L-15 Cterminus anti-CB 1 receptor (1:500, generously supplied by Dr. Ken Mackie, Indiana University, Bloomington, USA; see Köfalvi et al, 2005), rabbit anti-mGluR5 receptor (1:3000, from Upstate Biotechnology; see Rodrigues et al, 2005b) and goat anti-P2Y1 receptor (1:200, from Santa Cruz Biotechnology; see Rodrigues et al, 2005a). After four washing periods for 10 min with TBS-T containing 0.5% milk, the membranes were incubated with the alkaline phosphatase-conjugated anti-goat, anti-rabbit, anti-mouse or anti-guinea-pig secondary antibody (1:2000, from Amersham) in TBS-T containing 1% milk during 90 min at room temperature.…”

Section: Western Blot Analysismentioning

confidence: 99%

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Canas

Duarte

Rodrigues

et al. 2009

Neurobiology of Aging

125

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Please cite this article in press as: Canas, P.M., et al., Modification upon aging of the density of presynaptic modulation systems in the hippocampus, Neurobiol Aging (2008) Abstract Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A 1 and CB 1 receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A 2A receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory presynaptic modulation systems.

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“…The Isc/short-circuit current nulled out the spontaneous potential difference (PD) and was used as a measure of chloride secretion in the distal colon. (Modified from [25] by permission) P2Y 1 , P2Y 2 , and P2Y 4 receptors to inhibit glutamate release [91]; presynaptic P2Y 1 and P2Y 2 receptors also occur in the rat submucous plexus. A working model of the purinergic neural circuitry in the rat colon is shown in Fig.…”

Section: P2y 1 Receptors and Mucosal Stroking-evoked Neurosecretory Rmentioning

confidence: 99%

Purinergic receptors and gastrointestinal secretomotor function

Christofi

2008

Purinergic Signalling

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Secretomotor reflexes in the gastrointestinal (GI) tract are important in the lubrication and movement of digested products, absorption of nutrients, or the diarrhea that occurs in diseases to flush out unwanted microbes. Mechanical or chemical stimulation of mucosal sensory enterochromaffin (EC) cells triggers release of serotonin (5-HT) (among other mediators) and initiates local reflexes by activating intrinsic primary afferent neurons of the submucous plexus. Signals are conveyed to interneurons or secretomotor neurons to stimulate chloride and fluid secretion. Inputs from myenteric neurons modulate secretory rates and reflexes, and special neural circuits exist to coordinate secretion with motility. Cellular components of secretomotor reflexes variably express purinergic receptors for adenosine (A1, A2a, A2b, or A3 receptors) or the nucleotides adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP), uridine 5′-triphosphate (UTP), or uridine diphosphate (UDP) (P2X 1-7 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 12 receptors). This review focuses on the emerging concepts in our understanding of purinergic regulation at these receptors, and in particular of mechanosensory reflexes. Purinergic inhibitory (A 1 , A 3 , P2Y 12 ) or excitatory (A 2 , P2Y 1 ) receptors modulate mechanosensitive 5-HT release. Excitatory (P2Y 1 , other P2Y, P2X) or inhibitory (A 1 , A 3 ) receptors are involved in mechanically evoked secretory reflexes or "neurogenic diarrhea." Distinct neural (pre-or postsynaptic) and non-neural distribution profiles of P2X 2 , P2X 3 , P2X 5 , P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , or P2Y 12 receptors, and for some their effects on neurotransmission, suggests their role in GI secretomotor function. Luminal A 2b , P2Y 2 , P2Y 4 , and P2Y 6 receptors are involved in fluid and Cl -, HCO 3 -, K + , or mucin secretion. Abnormal receptor expression in GI diseases may be of clinical relevance. Adenosine A 2a or A 3 receptors are emerging as therapeutic targets in inflammatory bowel diseases (IBD) and gastroprotection; they can also prevent purinergic receptor abnormalities and diarrhea. Purines are emerging as fundamental regulators of enteric secretomotor reflexes in health and disease.

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Dual Presynaptic Control by ATP of Glutamate Release via Facilitatory P2X₁, P2X_2/3, and P2X₃and Inhibitory P2Y₁, P2Y₂, and/or P2Y₄Receptors in the Rat Hippocampus

Cited by 202 publications

References 49 publications

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Purinergic receptors and gastrointestinal secretomotor function

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