Dual coupling of heterologously‐expressed rat P2Y6 nucleotide receptors to N‐type Ca2+ and M‐type K+ currents in rat sympathetic neurones

Filippov, Alexander K.; Webb, Tania E.; Barnard, Eric A.; Brown, David A.

doi:10.1038/sj.bjp.0702356

Cited by 65 publications

(70 citation statements)

References 42 publications

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“…8, A and B). The extent of this effect matches the partial reduction found previously (19) with noradrenaline acting on the native adrenoceptors in these neurons under the same conditions. That effect was in other cases shown to be a voltage-dependent action due to released G␤␥ subunits inducing a gating shift of the channel (16,27,29).…”

Section: Table I Agonist and Antagonist Potencies Of Heterologously Esupporting

confidence: 72%

“…7A), the inhibition was 48.8 Ϯ 4.3% (n ϭ 14). This fraction of the population of these channels that is susceptible to P2Y 12 receptor-mediated inhibition is similar to that found for them with the other P2Y receptor subtypes studied (16,17,19). In control experiments (with neurons injected with the same vector carrying only the EGFP-cDNA) the inhibition of this Ca 2ϩ current by 2-MeSADP or 2-MeSATP, up to 10 M, was maximally 5.00 Ϯ 2.04% (n ϭ 9), the same non-significant change as was seen at 10 M agonist with neurons not injected at all.…”

Section: Downloaded Fromsupporting

confidence: 56%

“…8, A and B). Effects on the M-current K ϩ channel, which has been found previously (16,19) to be blocked by the activation of other P2Y receptors, were also studied here. This current was unaffected by stimulation of the P2Y12 receptors expressed in these neurons (Table II).…”

Section: Table I Agonist and Antagonist Potencies Of Heterologously Ementioning

confidence: 99%

“…For revealing receptor/ channel couplings, this system, as we have shown previously (16,17,19,23) with other P2Y subtypes, has advantages over the usual transfection of immortalized cell lines; only the expressing cells are recorded, and coupling through endogenous ion channels in a native neuron can be analyzed. Furthermore, at the stage at which these cells are used there is no significant expression of endogenous P2Y receptors (16,17), and native P2Y 12 receptors are also now being excluded by the controls as shown in Fig.…”

Section: Downloaded Frommentioning

confidence: 99%

“…Whole-cell currents through the GIRK channels in fluorescent cells were recorded as described (18) but at ϳ20°C, in perforated patch mode, with external 6 mM KCl and with a 200-ms range for the standard ramp voltage commands applied. Currents through the N-type Ca 2ϩ channels carried by 5 mM Ba 2ϩ were recorded and identified as described previously (19). The currents were routinely evoked every 20 s, for a period of 50 ms, by a depolarizing test pulse from Ϫ90 to 0 mV; they are shown as leakcorrected by subtracting the current remaining after substituting 5 mM Co 2ϩ for Ba 2ϩ in the external solution (as described in Ref.…”

Section: Injections Of Rat Superior Cervical Ganglion (Scg) Neurons Amentioning

confidence: 99%

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Characterization and Channel Coupling of the P2Y12Nucleotide Receptor of Brain Capillary Endothelial Cells

Simon¹,

Filippov²,

Göransson³

et al. 2002

Journal of Biological Chemistry

103

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B10 cells are an endothelial clonal line derived spontaneously by culture and selection of rat brain microvascular endothelial cells (1), a source of considerable pharmacological potential. The B10 cells respond to extracellular adenine (but not uracil) nucleotides with intracellular Ca 2ϩ mobilization, mediated by a G-protein-coupled P2Y 1 receptor (2). Whereas the known rat P2Y 1 receptor cDNA could be isolated from the B10 cells (2), no transcript for any other then-known P2Y receptor subtype was detectable in them. However, the B10 cells were found to exhibit another second messenger response, namely the inhibition of stimulated adenylyl cyclase, but with a nucleotide agonist specificity very similar to that of the P2Y 1 receptor (2). It was further demonstrated (3) that selective antagonists of the P2Y 1 receptor, such as adenosine 3Ј-phosphate 5Ј-phosphate, were unable to affect that response, although it showed high sensitivity to 2-propylthio-D-␤,␥-difluoromethylene-ATP (AR-C66096), 1 a specific antagonist (4, 5) of the adenylyl cyclase-inhibitory P2Y T or "P2T" receptor for ADP, which was known as an important functional component of blood platelets. That study (3) demonstrated that a second P2Y receptor activity is present in the B10 cell, with some of its functional features in common with the platelet P2Y T receptor.Recently, a cDNA encoding a nucleotide receptor with a novel seven-transmembrane sequence was identified independently by two groups, starting from a human platelet cDNA library or an orphan human DNA sequence, and shown to be distantly but significantly related to the known P2Y receptors (6, 7). This was designated as the P2Y 12 receptor. Its amino acid sequence lies on a previously unrecognized separate branch of the P2Y family (8). It was characterized in both studies to show its adenine nucleotide specificity and its inhibition of forskolin-stimulated adenylyl cyclase, in which it corresponds to the platelet P2Y T receptor (6, 7). That human P2Y 12 receptor cDNA was expressed again in cell line hosts by other groups, confirming the reported series of agonists but with higher potencies in the cAMP decrease (9) and showing their affinities by competition with the binding of radiolabeled 2-MeSADP (9, 10). In the original identification of the human P2Y 12 receptor, a similar cDNA was also derived from a rat platelet library (6), and its RNA was shown to express in Xenopus oocytes, but this receptor was not further characterized.The question, therefore, obviously arises as to whether the cyclase inhibitory receptor for adenine nucleotides of the B10 capillary endothelial cell is in fact the P2Y 12 receptor. However, this cannot necessarily be assumed, because the P2T receptor has commonly been described in the literature as specific to the platelet (11,12). Furthermore, the adenylyl cyclase-inhibitory P2Y receptor activity in the B10 cell differs in an important

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Section: Table I Agonist and Antagonist Potencies Of Heterologously Esupporting

confidence: 72%

Section: Downloaded Fromsupporting

confidence: 56%

Section: Table I Agonist and Antagonist Potencies Of Heterologously Ementioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Section: Injections Of Rat Superior Cervical Ganglion (Scg) Neurons Amentioning

confidence: 99%

See 3 more Smart Citations

Characterization and Channel Coupling of the P2Y12Nucleotide Receptor of Brain Capillary Endothelial Cells

Simon¹,

Filippov²,

Göransson³

et al. 2002

Journal of Biological Chemistry

103

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Mechanisms of adenosine 5?-triphosphate-induced dopamine release in the rat nucleus accumbens in vivo

Krügel

Kittner

Illéš

2001

Synapse

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Modulation of voltage‐ and ligand‐gated ion channels by neuronal P2Y receptors

Wirkner

Köles

Fürst

et al. 2003

Drug Development Research

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The present review summarizes data about the properties, distribution, and effects of neuronal P2Y receptors. Extracellular nucleotide receptors can be classified into two types belonging either to the P2X (ligand-gated cationic channels) or the P2Y type (G protein-coupled receptors). Neuronal P2Y receptors comprise five cloned and functionally defined classes of which P2Y 1 , P2Y 6 , P2Y 11 , P2Y 12 , and P2Y 13 occur in the central nervous system. Various types of P2Y receptors stimulate inwardly rectifying potassium channels, positively or negatively modulate the high-voltage activated Ca 2+ current and increase the intracellular free Ca 2+ concentration in neuronal preparations. Moreover, in a subpopulation of pyramidal cells of the rat prefrontal cortex (PFC), the P2Y 2 receptor potentiates the function of a ligand-gated cationic channel, the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. This effect is G protein-mediated and utilizes the phospholipase C/inositol 1,4,5-trisphosphate/ Ca 2+ /calmodulin kinase II pathway. It appears that P2Y 2 receptors situated at astrocytes release glutamate, which in turn modulates NMDA receptors of neighbouring neurons via stimulation of group I metabotropic glutamate receptors. In contrast, P2Y 1 receptors inhibit the conductance of NMDA receptor-channels in all PFC pyramidal cells investigated. This effect is fast in onset and does not depend on G protein activation. It is suggested that P2Y 1 receptors alter the function of NMDA receptors by a direct protein-protein coupling in the membrane. Because ATP and dopamine are supposed to be coreleased from dopaminergic fibers onto layer V pyramidal cells, both neurotransmitters may interact with the neuronal NMDA receptor. Hence, D 1 dopamine receptors and P2Y 1 /P2Y 2 receptors may be involved in the fine tuning of higher order cognitive functions including learning and memory. Drug Dev. Res. 59:49-55, 2003.

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Dual coupling of heterologously‐expressed rat P2Y₆ nucleotide receptors to N‐type Ca²⁺ and M‐type K⁺ currents in rat sympathetic neurones

Cited by 65 publications

References 42 publications

Characterization and Channel Coupling of the P2Y12Nucleotide Receptor of Brain Capillary Endothelial Cells

Characterization and Channel Coupling of the P2Y12Nucleotide Receptor of Brain Capillary Endothelial Cells

Mechanisms of adenosine 5?-triphosphate-induced dopamine release in the rat nucleus accumbens in vivo

Modulation of voltage‐ and ligand‐gated ion channels by neuronal P2Y receptors

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