ATP receptors

doi:10.1016/0959-4388(94)90095-7

Current Opinion in Neurobiology

Volume 4, Issue 3, June 1994, Pages 347-352

https://doi.org/10.1016/0959-4388(94)90095-7 Get rights and content

Abstract

ATP receptors continue to be found in an ever wider range of tissues in the brain and the periphery. Much of the recent research on these receptors focuses on features that would distinguish ATP-mediated excitatory synaptic transmission from that mediated through glutamate or acetylcholine receptors. These features include kinetics of the synaptic currents, voltage-independent calcium permeability of the underlying channels, interactions with adenosine, and various direct modulators of the ATP-gated ion channel.

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The current study used a single trial bead discrimination task for the young chick to ascertain if inhibitors of P2 purinergic receptors would impair memory retention. Suramin and PPADS provided similar retention profiles. Loss of memory retention was evident by 60 min post-training. Both drugs caused persistent memory loss which was still evident 24 h post-training. These findings suggest that P2 receptors have a role in memory processing.
Ethanol Alters the Physiology of Neuron-Glia Communication
2009, International Review of Neurobiology
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In astrocytes, Ca2+ signaling is mostly involved in activation of either type of membrane receptor. Adenosine 5′-triphosphate, adenosine and related substances act as neurotransmitters in the CNS to control important physiological functions through the activation of their so named purinoreceptors (Edwards, 1994; Fredholm et al., 2005; Neary et al., 2004; Tran et al., 2008). As for glutamate receptors, purinoreceptors can be subdivided into ionotropic and metabotropic receptors.
In the central nervous system (CNS), both neurones and astrocytes play crucial roles. On a cellular level, brain activity involves continuous interactions within complex cellular circuits established between neural cells and glia. Although it was initially considered that neurones were the major cell type in cerebral function, nowadays astrocytes are considered to contribute to cerebral function too. Astrocytes support normal neuronal activity, including synaptic function, by regulating the extracellular environment with respect to ions and neurotransmitters. There is a plethora of noxious agents which can lead to the development of alterations in organs and functional systems, and that will end in a chronic prognosis. Among the potentially harmful external agents we can find ethanol consumption, whose consequences have been recognized as a major public health concern. Deregulation of cell cycle has devastating effects on the integrity of cells, and has been closely associated with the development of pathologies which can lead to dysfunction and cell death. An alteration of normal neuronal–glial physiology could represent the basis of neurodegenerative processes. In this review we will pay attention on to the recent findings in astrocyte function and their role toward neurons under ethanol consumption.
ATP can stimulate exocytosis in rat brown adipocytes without apparent increases in cytosolic Ca<sup>2+</sup> or G protein activation
1999, Biophysical Journal
Extracellular ATP activates large increases in cell surface area and membrane turnover in rat brown adipocytes (Pappone, P. A., and Lee, S. C. 1996. J. Gen. Physiol. 108:393–404). We used whole-cell patch clamp membrane capacitance measurements of membrane surface area concurrently with fura-2 ratio imaging of intracellular calcium to test whether these purinergic membrane responses are triggered by cytosolic calcium increases or G protein activation. Increasing cytosolic calcium with adrenergic stimulation, calcium ionophore, or calcium-containing pipette solutions did not cause exocytosis. Extracellular ATP increased membrane capacitance in the absence of extracellular calcium with internal calcium strongly buffered to near resting levels. Purinergic stimulation still activated exocytosis and endocytosis in the complete absence of intracellular and extracellular free calcium, but endocytosis predominated. Modulators of G protein function neither triggered nor inhibited the initial ATP-elicited capacitance changes, but GTPγS or cytosolic nucleotide depletion did reduce the cells’ capacity to mount multiple purinergic responses. These results suggest that calcium modulates purinergically-stimulated membrane trafficking in brown adipocytes, but that ATP responses are initiated by some other signal that remains to be identified.
Expression of the P2X<inf>7</inf>-receptor subunit in neurons of the rat retina
1998, Molecular Brain Research
Despite the considerable evidence of signaling by extracellular nucleotides in other sensory systems, few studies have been undertaken in the eye. Molecular and immunohistochemical methods were used to demonstrate the expression and cellular localization of the P2X₇ receptor subunit in the retina and choroid. RT-PCR was used for the detection of P2X₇ subunit mRNA in the rat of different postnatal developmental stages (P23–P210) and revealed the presence of P2X₇-mRNA in the retina, but not in the choroid. In the adult rat retina, immunolabelling for P2X₇ was detected in a number of cells in the inner nuclear layer (INL) and ganglion cell layer (GCL), suggesting different types of amacrine cells and ganglion cells. These results demonstrate for the first time the expression of the P2X₇ receptor in the mammalian retina and furthermore in distinct neuronal cell populations. Our data suggest that extracellular ATP may provide both neuromodulatory and trophic influences on visual processing.
Depression of C fiber-evoked activity by intrathecally administered reactive red 2 in rat thalamic neurons
1998, Brain Research
To investigate the possible role of spinal purinoceptors in nociception, the potent P₂-purinoceptor antagonist reactive red 2 was studied in rats under urethane anesthesia in which nociceptive activity was elicited by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurons in the ventrobasal complex of the thalamus. Intrathecal (i.t.) application of reactive red 2 (6–200 μg) caused a dose-dependent reduction of the evoked activity in thalamic neurons. The estimated ED₅₀ was 30 μg, and the maximum depression of nociceptive activity amounted to about 70% of the control activity at a dose of 100 μg. Morphine, administered i.t. at a maximally effective dose (80 μg), inhibited the evoked nociceptive activity by only up to 55% of the control activity. An i.t. co-injection of reactive red 2 (100 μg) and morphine (80 μg) caused a maximum reduction of the evoked thalamic activity by up to 85% of the control activity, thus, exceeding significantly the effect elicited by either drug alone. Similarly, i.t. co-injection of almost equipotent dosages of reactive red 2 (30 μg) and morphine (30 μg) caused a maximum reduction of the evoked activity by up to 72% of the control activity, which again exceeded significantly the effect of either drug alone. The results suggest that in rats reactive red 2 exerts antinociception by blockade of P₂-purinoceptors in the spinal cord and, hence, support the idea that ATP may play an important role in spinal transmission of nociceptive signals. An activation of the spinal opioid system does not seem to contribute to the effect of reactive red 2 but might act additive or even synergistically with its antinociceptive action.
Fluorescence imaging of Na<sup>+</sup> influx via P2X receptors in cochlear hair cells
1998, Hearing Research
The adenosine 5′-triphosphate (ATP)-activated membrane conductance, mediated by P2X receptors, was examined in isolated guinea-pig cochlear inner and outer hair cells. Photo-activated release of caged-ATP elicted a 30-ms latency inwardly rectifying non-selective cation conductance, blocked by the P2X receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10–100 μM), consistent with the direct activation of ATP-gated ion channels. A K_(Ca) conductance in the inner hair cells (IHC), activated by the entry of Ca²⁺ through the ATP-gated ion channels, was blocked by including 10 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) in the internal solution. Real-time confocal slit-scanning fluorescence imaging of Na⁺ influx through the ATP-gated ion channels was performed using the dye Sodium Green™ with simultaneous whole-cell recording of membrane currents. The Na⁺ entry was localized to the endolymphatic surface, with the increase in [Na⁺]_i detected within approximately 200 ms of the onset of the inward current response. Within 600 ms Na⁺ had diffused throughout the cell cytoplasm with the exception of the subnuclear region of the outer hair cells. Correlation of voltage-clamp measurements of Na⁺ entry with regional increases in Na⁺-induced fluorescence demonstrated ATP-induced increases in intracellular Na⁺ in excess of 45 mM within 4 s. These data provide direct evidence for the Na⁺ permeability of the ATP-gated ion channels as well as independent evidence for the localization of P2X receptors at the endolymphatic surface of the sensory hair cells. The localization of the ATP-gated ion channels to the apical surface of the hair cells supports an ATP-mediated modulation of `silent' K⁺ current across the cochlear partition which could regulate hearing sensitivity by controlling the transcellular driving force for both mechanoelectrical and electromechanical transduction in hair cells.

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ATP receptors

Abstract

Trends Pharmacol Sci

FEBS Lett

FEBS Lett

J Physiol (Lond)

Br Pharmacol

Br J Pharmacol

J Physiol (Lond)

Am J Physiol

ProJ Pharmacol

J Neurochem

Invited Review-Signal Trans duction via P2-Purinergic Receptors for Extracelular ATP and Other Nucleotides

Am J Physiol

Extracellular ATP and Cell Signalling

Biochim Biophys Acta

ATP-Induced Calcium Transient in Cultured Rat Aortic Smooth Muscle Cells

J Biochem (Tokyo)

ATP and Its Metabolite Adenosine Act Synergistically to Mobilise Intracellular Calcium via the Formation of Inositol 1,4,5-Triphosphate in a Smooth Muscle Cell Line

J Biol Chem

Neuronal ‘Nucleotide’ Receptor Linked to Phospholipase-C and Phospholipase-D — Stimulation of PC-12 Cells by ATP Analogues and UTP

Mol Pharmacol

Block by Calcium of ATP Activated Channels in Pheochromocytoma Cells

J Gen Physiol

Expression Cloning of an ATP Receptor from Mouse Neuroblastoma Cells

Cloning and Functional Expression of a Brain GProtein-Coupled ATP Receptor

FEBS Lett

ATP-Activated Channels in Rat and Bullfrog Sensory Neurons: Concentration Dependence and Kinetics

J Neurosci

ATP-Gated Current in Dissociated Rat Nucleus Solitarii Neurons

J Neurophysiol

ATP- and Acetylcholine-Activated Channels Co-Existing in Cell-Free Membrane Patches from Rat Sympathetic Neuron

Neurosci Lett

ATP Receptor-Mediated Synaptic Currents in the Central Nervous System

Nature

ATP Mediates Fast Synaptic Transmission in Mammalian Neurons

Nature

Invited Review-Signal Trans duction via P₂-Purinergic Receptors for Extracelular ATP and Other Nucleotides