The adenosine receptor‐mediated inhibition of noradrenaline release possibly involves a N‐protein and is increased by α<sub>2</sub>‐autoreceptor blockade

Allgaier, Clemens; Hertting, G.; Kügelgen, Oda V.

doi:10.1111/j.1476-5381.1987.tb08970.x

Cited by 66 publications

(23 citation statements)

References 35 publications

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“…Thus, overflow of noradrenaline evoked by electrical stimulation can be interpreted as noradrenaline release. cx2-Adrenoceptors were also blocked, so any interference of auto-inhibition mediated by prejunctional 2-autoreceptors with the effect of purinoceptor agonists and antagonists was avoided (see Enero & Saidman, 1977;Allgaier et al, 1987;Limberger et al, 1988;Guimaraes et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Gonçalves

Queiróz

1996

British J Pharmacology

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1 The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2 The A,-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the Aladenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 gM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 gM) and suramin (100 gM).3 Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(pnitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 gM) increased evoked noradrenaline overflow as did suramin, a nonselective P2-antagonist.4 It is concluded that, in rat tail artery, inhibitory (Al and P2y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory Al purinoceptors seems to be prevented by adenosine uptake.

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Section: Discussionmentioning

confidence: 99%

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Gonçalves

Queiróz

1996

British J Pharmacology

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“…The fractional rate of tritium outflow (5 min)-' was calculated as tritium outflow per 5 min/tritium content in the slice at the start of the respective S min period (Hertting et al, 1980;Allgaier et al, 1987). The stimulation-evoked overflow of tritium was calculated by subtraction of the basal outflow from the total outflow of tritium.…”

Section: Calculation Of Release Datamentioning

confidence: 99%

Protein kinase C activation and α₂‐autoreceptor‐modulated release of noradrenaline

Allgaier

Hertting

Huang

et al. 1987

British J Pharmacology

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1Effects of phorbol esters on the evoked noradrenaline release were studied in slices of the rabbit hippocampus, labelled with [3HJ-noradrenaline, superfused continuously with a medium containing the reuptake inhibitor cocaine and stimulated electrically for 2 min (stimulation parameters: 2 ms, 24mA, 5Vcm-', 3 or 0.3Hz).2 The electrically-evoked overflow of [3H]-noradrenaline in the slices was increased in a concentration-dependent manner by the protein kinase C (PKC) activators 12-0-tetradecanoylphorbol 13-acetate (TPA) and 4f-phorbol 12,13-dibutyrate (4p-PDB). Phorbol esters, which do not activate PKC, 4-0-methyl-TPA and 4a-PDB, showed no effect on neurotransmitter release. The effect of4P-PDB was abolished in the presence of tetrodotoxin and in the absence of calcium. The PKC inhibitor polymyxin B inhibited the evoked noradrenaline release.3 In the presence of 4P-PDB the inhibitory effects of the o2-adrenoceptor agonist clonidine or the facilitatory effects ofthe z2-adrenoceptor antagonist yohimbine seemed to be modified only by changes in the concentration of noradrenaline in the synaptic region. At a stimulation frequency of 3 Hz the inhibitory action of clonidine was reduced whereas the facilitatory effect of the yohimbine was even slightly enhanced by the phorbol ester. At 0.3 Hz and in the presence of 4P-PDB the effect of clonidine remained and that of yohimbine was strongly enhanced. 4 Pretreatment of the slices with islet-activating protein or N-ethylmaleimide significantly reduced the enhancement of noradrenaline release caused by 4P-PDB. It is possible that a regulatory N-protein is involved in steps following PKC activation. 5 These results suggest that PKC participates in the mechanism of action-potential-induced noradrenaline release from noradrenergic nerve terminals of the rabbit hippocampus and that effects on the autoinhibitory feedback system were not responsible for the 4P-PDB-induced increase of neurotransmitter release.

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“…These neuroprotective effects are mediated primarily by A 1 receptors. The activation of presynaptic A 1 receptors inhibits synaptic transmission in hippocampal [Ribeiro, 1995;Coelho et al, 2000] and cerebral cortical neurons [Phillis et al, 1997] and leads to a reduction of neurotransmitter release [Dunwiddie and Haas, 1985;Fredholm and Dunwiddie, 1988;Allgaier et al, 1987;de Mendonca and Ribeiro, 1993;Vazquez and Sanchez-Prieto, 1997]. Activation of postsynaptic A 1 receptors induces hyperpolarization by an activation of ATP-sensitive potassium channels in locus coeruleus neurons [Nieber et al, 1995] and by a voltage-dependent chloride conductance in hippocampal neurons [Mager et al, 1990].…”

Section: Introductionmentioning

confidence: 99%

A₃receptors in cortical neurons: Pharmacological aspects and neuroprotection during hypoxia

Lewerenz

Hentschel

Vissiennon

et al. 2003

Drug Development Research

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Adenosine, which is released under pathophysiological conditions such as hypoxia or ischemia, is involved in a variety of regulatory processes related to neuroprotection. Major advances in the research on neuronal adenosine receptors have provided a better understanding of the mechanisms underlying the neuroprotective effects during hypoxia. The therapeutic potential of adenosine was recognized several years ago, but only the development of stable and selective adenosine receptor agonists and antagonists has offered novel approaches for the pharmacological manipulation of the receptor activity. To date, four G protein coupled receptors have been cloned and identified in the central nervous system: A 1 , A 2A , A 2B , and A 3. The neuroprotective effects of adenosine are mediated primarily by the activation of A 1 receptors. Knowledge of the physiological role of A 3 receptors in the brain is still limited. This article focuses on new evidences referring to possible functions of A 3 receptors in the CNS, especially the role during hypoxia. Electrophysiological investigations on brain slices give us new insights concerning mechanisms of synaptic modulation. The data from pyramidal cells of the rat cingulate cortex show that a high level of endogenous adenosine (occuring during hypoxia) activates A 3 receptors, which mediates a depression of the synaptic transmission. The A 3 receptors inhibit the glutamate release additionally to and independently from the A 1 receptors. The two distinct mechanisms of synaptic modulation contribute to the neuroprotective action of adenosine during hypoxia and offer new approaches for therapeutic strategies. Drug Dev. Res. 58:420-427, 2003.

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The adenosine receptor‐mediated inhibition of noradrenaline release possibly involves a N‐protein and is increased by α₂‐autoreceptor blockade

Cited by 66 publications

References 35 publications

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Protein kinase C activation and α₂‐autoreceptor‐modulated release of noradrenaline

A₃receptors in cortical neurons: Pharmacological aspects and neuroprotection during hypoxia

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The adenosine receptor‐mediated inhibition of noradrenaline release possibly involves a N‐protein and is increased by α2‐autoreceptor blockade

Cited by 66 publications

References 35 publications

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y‐ and facilitatory A2A‐purinoceptors

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y‐ and facilitatory A2A‐purinoceptors

Protein kinase C activation and α2‐autoreceptor‐modulated release of noradrenaline

A3receptors in cortical neurons: Pharmacological aspects and neuroprotection during hypoxia

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The adenosine receptor‐mediated inhibition of noradrenaline release possibly involves a N‐protein and is increased by α₂‐autoreceptor blockade

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Protein kinase C activation and α₂‐autoreceptor‐modulated release of noradrenaline

A₃receptors in cortical neurons: Pharmacological aspects and neuroprotection during hypoxia