Pharmacological characterization of P2 purinoceptor types in rat locus coeruleus neurons

Fröhlich, Rainer; Boehm, Stefan; Illéš, Peter

doi:10.1016/s0014-2999(96)00612-7

Cited by 55 publications

(33 citation statements)

References 34 publications

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“…Furthermore, it should be emphasized that in contrast to the P2 receptor antagonists suramin and reactive blue 2 no direct glutamate antagonistic properties were found for PPADS (Fröhlich et al, 1996;Motin and Bennett 1995;Gu et al, 1998). The anxiolytic-like effects of ADPbS were also abolished after pretreatment with MRS 2179, which acts as a specific P2Y 1 receptor antagonist (Boyer et al, 1998).…”

Section: Discussionmentioning

confidence: 96%

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Kittner

Franke

Fischer

et al. 2002

Neuropsychopharmacol

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(ADPbS), the P2X 1,3 receptor agonist a,b-methylene ATP (a,bmeATP), the unspecific P2 receptor antagonist pyridoxalphosphate-6-azopheny l-2 0 ,4 0 -disulfonic acid (PPADS), and the specific P2Y 1 receptor antagonist N 6 -methyl-2 0 -deoxyadenosine-3 0 ,5 0 -bisphosphate (MRS 2179) on the elevated plus-maze behavior of the rat were investigated. All tested compounds were given intracerebroventricularly (0.5 ml). ADPbS (50 and 500 fmol) produced an anxiolytic-like behavioral profile reflected by an increase of the open arm exploration. The anxiolytic-like effects were antagonized by pretreatment with PPADS (5 pmol) or MRS 2179 (5 pmol). Both compounds caused anxiogenic-like effects when given alone. Furthermore, the anxiolytic-like effects of ADPbS could be antagonized by pretreatment with the nitric oxide synthase (NOS) inhibitor N w -nitro-L-arginine methyl ester (L-NAME). In addition, the anxiogenic-like effects of PPADS were reversed by the pretreatment with L-arginine (500 pmol), which is the natural substrate for NOS, but not by D-arginine (500 pmol), which is not. Immunofluorescence staining revealed the presence of P2Y 1 receptors on neurons in different brain regions such as hypothalamus, amygdala, hippocampus and the periaqueductal gray. Furthermore, the colocalization of P2Y 1 receptors and neuronal NOS (nNOS) on some neurons in these regions could be demonstrated. The highest density of P2Y 1 -and nNOS-immunoreactivity was detected in the dorsomedial hypothalamic nucleus. Taken together, the present results suggest that P2Y 1 receptors are involved in the modulation of anxiety in the rat. The anxiolytic-like effects after stimulation of P2Y 1 receptors seem to be in close connection with the related nitric oxide production.

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Section: Discussionmentioning

confidence: 96%

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Kittner

Franke

Fischer

et al. 2002

Neuropsychopharmacol

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“…Locus coeruleus neurons of the rat are equipped with ATP-sensitive P2X and P2Y-like receptors, the activation of which facilitates the discharge of spontaneous action potentials (Frohlich et al, 1996). The outflow of noradrenaline from brain slices, including the hippocampus, is modulated by inhibitory A 1 adenosine receptors (Jonzon and Fredholm, 1984) and P2Y-like receptors (Koch et al, 1997).…”

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confidence: 99%

P2X Receptor Activation Elicits Transporter-Mediated Noradrenaline Release from Rat Hippocampal Slices

Papp¹,

Balázsa²,

Köfalvi³

et al. 2004

J Pharmacol Exp Ther

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This study was designed to test the hypothesis of whether activation of presynaptic P2X receptor-gated ion channels elicits noradrenaline release from central catecholaminergic terminals. ATP, ␣,␤-methylene-adenosine 5Ј-triphosphate (␣,␤-methyleneATP), and ADP elicited concentration-dependent [ 3 H]noradrenaline outflow from superfused rat hippocampal slices with the following rank order of agonist potency: ␣,␤-methyleneATP Ͼ ATP Ͼ ADP. Among P2 receptor antagonists, pyridoxal-phosphate-6-azophenyl-2Ј,4Ј-disulphonic acid (30 M), 4,4Ј,4ЈЈ,4ЈЈЈ-[carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid (100 nM), and 8,8Ј-[carbonybis(imino-3,1-phenylenecarbonylimino)]bis1,3,5-naphthalenetrisulphonic acid (10 M) significantly inhibited the outflow of [ 3 H]noradrenaline, evoked by ATP, whereas Brilliant Blue G (100 nM), 2Ј-deoxy-N 6 -methyladenosine 3Ј,5Ј-bisphosphate tetraammonium (10 M), the A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (250 nM), and the A 2A receptor antagonist 3,7-dimethyl-1-propargylxanthine (250 nM) were ineffective. Pretreatment with the G i protein inhibitor pertussis toxin (2.5 g/ml) did not change the effect of ATP on [ 3 H]noradrenaline outflow. In contrast, a decrease in extracellular pH from 7.4 to 6.6 significantly attenuated the response by ATP. When extracellular Na ϩ was replaced by choline chloride and in the presence of the noradrenaline uptake inhibitor desipramine (10 M), the ATP-evoked [ 3 H]noradrenaline outflow was almost completely abolished, indicating that its underlying mechanism is the sodium-dependent reversal of the noradrenaline transporter. Reverse transcription-polymerase chain reaction analysis revealed that mRNA encoding P2X 1 , P2X 2 , P2X 3 , P2X 4 , P2X 6 , P2X 7 , and P2Y 1 receptor subunits were expressed in the brainstem containing catecholaminergic nuclei projecting to the hippocampus, whereas mRNA encoding P2X 5 , P2Y 2 , P2Y 4 , and P2Y 6 receptors were absent. Taken together, these results indicate that noradrenergic terminals of the rat hippocampus are equipped with presynaptic facilitatory P2X receptors, displaying a pharmacological profile similar to homomeric P2X 1 and P2X 3 receptors.

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“…These CNS regions include: prepiriform cortex (Weisman et al, 1996), hippocampus (Inoue et al, 1995(Inoue et al, , 1996, medial habenula (Edwards et al, 1992), supraoptic nucleus (Day et al, 1993;Hiruma and Bourque, 1995), locus coeruleus Fröhlich et al, 1996), mesencephalic trigeminal nucleus (Cook et al, 1997;Khakh et al, 1997), medial vestibular nucleus , rostral ventrolateral medulla (Sun et al, 1992), nucleus tractus solitarius (Ergene et al, 1994), dorsal motor nucleus of vagus (Nabekura et al, 1995), hypoglossal nucleus (Funk et al, 1997), and spinal cord (Driessen et al, 1994;Salter and Hicks, 1994;Bardoni et al, 1997).…”

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confidence: 99%

Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system

et al. 1999

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The distribution of the P2X2 receptor subunit of the adenosine 5′‐triphosphate (ATP)‐gated ion channels was examined in the adult rat central nervous system (CNS) by using P2X2 receptor‐specific antisera and riboprobe‐based in situ hybridisation. P2X2 receptor mRNA expression matched the P2X2 receptor protein localisation. An extensive expression pattern was observed, including: olfactory bulb, cerebral cortex, hippocampus, habenula, thalamic and subthalamic nuclei, caudate putamen, posteromedial amygdalo‐hippocampal and amygdalo‐cortical nuclei, substantia nigra pars compacta, ventromedial and arcuate hypothalamic nuclei, supraoptic nucleus, tuberomammillary nucleus, mesencephalic trigeminal nucleus, dorsal raphe, locus coeruleus, medial parabrachial nucleus, tegmental areas, pontine nuclei, red nucleus, lateral superior olive, cochlear nuclei, spinal trigeminal nuclei, cranial motor nuclei, ventrolateral medulla, area postrema, nucleus of solitary tract, and cerebellar cortex. In the spinal cord, P2X2 receptor expression was highest in the dorsal horn, with significant neuronal labeling in the ventral horn and intermediolateral cell column. The identification of extensive P2X2 receptor immunoreactivity and mRNA distribution within the CNS demonstrated here provides a basis for the P2X receptor antagonist pharmacology reported in electrophysiological studies. These data support the role for extracellular ATP acting as a fast neurotransmitter at pre‐ and postsynaptic sites in processes such as sensory transmission, sensory‐motor integration, motor and autonomic control, and in neuronal phenomena such as long‐term potentiation (LTP) and depression (LTD). Additionally, labelling of neuroglia and fibre tracts supports a diverse role for extracellular ATP in CNS homeostasis. J. Comp. Neurol. 407:11–32, 1999. © 1999 Wiley‐Liss, Inc.

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Pharmacological characterization of P2 purinoceptor types in rat locus coeruleus neurons

Cited by 55 publications

References 34 publications

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

P2X Receptor Activation Elicits Transporter-Mediated Noradrenaline Release from Rat Hippocampal Slices

Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system

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