A2 adenosine receptors: their presence and neuromodulatory role in the central nervous system

Latini, Serena; Pazzagli, Marta; Pepeu, Giancarlo; Pedata, Felicita

doi:10.1016/0306-3623(96)00044-4

Cited by 79 publications

(44 citation statements)

References 81 publications

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“…A 2A -receptors could be activated either with a specific agonist (CGS 21680) or by increasing the concentration of the endogenous transmitter [46,[60][61][62]66]. In our hands, both actions were blocked by the highly selective A 2A -receptor antagonist, SCH 58261, suggesting specificity.…”

Section: +mentioning

confidence: 52%

“…40-120 nM [50][51][52][53][54][55], while micromolar concentrations are reached during more intense neuronal discharge [52,[56][57][58]. Low [basal] adenosine concentrations stimulate A 1 -receptors [46,59,60], while high concentrations activate A 2A -receptors [37,45,46,[60][61][62]. Taken together, these facts explain why the results of the sequential activation of A 1 -receptors on A 2A -receptors activation was easily observed in dissociated cells taking Ca 2+ -currents as effectors (reporters).…”

Section: Discussionmentioning

confidence: 94%

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Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons

Hernández-González

Hernández-Flores

Prieto

et al. 2013

Purinergic Signalling

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Section: +mentioning

confidence: 52%

Section: Discussionmentioning

confidence: 94%

Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons

Hernández-González

Hernández-Flores

Prieto

et al. 2013

Purinergic Signalling

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“…Thus, it is possible that the effect of D 2 receptors on cAMP accumulation is relatively small compared to the basal level of AC activation and therefore remains hidden in a given system. One possibility to decrease the non-dopaminergic signal is to use CGS21680 for the activation of AC via adenosine A 2A receptors (20), colocalized with D 2 receptors in rat striatum (31). The antagonistic influence of heterodimerization of these receptors may of course decrease the response, but would not eliminate it (32).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Adenylyl Cyclase Activity in Rat Striatal Homogenate by Dopaminergic Receptors

2008

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Abstract. We have characterized the modulation of adenylyl cyclase (AC) activity by ligands of dopaminergic receptors in rat striatal homogenate and compared the results with receptorligand binding affinities. Despite the fact that rat striatum contains high level of both dopamine D 1 and D 2 receptors, only the D 1 -specific AC activation by agonists could be determined. All D 1 -receptor agonists (dopamine, dihydrexidine, and A 77636) used were able to increase cAMP accumulation in a concentration-dependent manner, while D 1 -receptor antagonists (SCH23390, SKF83566, and butaclamol) blocked the effects induced by the aforementioned agonists. At the same time, the D 2 -receptor agonist quinpirole and antagonist sulpiride had no effect on cAMP accumulation in striatal homogenate neither on the basal level nor on the activated level of AC, while inhibited [

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“…When viewed in this light, it becomes important to determine which receptors colocalize with dopamine D2 receptor positive cells and may be coupled to an increase in cAMP. Candidate receptors for which evidence of colocalization exist include 5HT6 and 5HT4 receptors (33) and the adenosine A2 receptor (34,35). Blockade of adenosine A2 receptors can prevent haloperidol-induced catalepsy and NT gene expression in the DLST in rats (R. Ward and D.M.D., unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice

Adams

Brandon

Chartoff

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

100

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The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the dorsal lateral region of the striatum and produces an acute cataleptic response in rodents that correlates with the motor side effects of haloperidol in humans. Mice harboring a targeted disruption of the RII␤ subunit of protein kinase A have a profound deficit in cAMP-stimulated kinase activity in the striatum. When treated with haloperidol, RII␤ mutant mice fail to induce either c-fos or neurotensin mRNA and the acute cataleptic response is blocked. However, both wild-type and mutant mice become cataleptic when neurotensin peptide is directly injected into the lateral ventricle, demonstrating that the kinase deficiency does not interfere with the action of neurotensin but rather its synthesis and release. These results establish a direct role for protein kinase A as a mediator of haloperidol induced gene induction and cataleptic behavior.Antipsychotic drugs are a group of chemically diverse compounds that are used in the treatment of severe psychiatric disorders. The efficacy of haloperidol, the prototypic antipsychotic agent, in the treatment of the symptoms of schizophrenia is thought to result, at least in part, from its ability to bind to and antagonize dopamine D2-like receptors (1, 2) leading to an increase in cAMP (3). However, the pathways that connect the changes in cAMP levels to either therapeutic or toxic effects remain unclear.Medium spiny neurons in the striatum express either D1 or D2 receptors (4). The D1 receptor is coupled via Gs to a stimulation of cAMP synthesis whereas the D2 receptor is Gi coupled and could lead to an inhibition of adenylate cyclase activity and a decrease in intracellular cAMP. D2 receptors are also coupled to the activation of K ϩ channels via the ␤␥ subunits (5). Acute haloperidol administration leads to changes in neuropeptide gene expression in the striatum. One of the genes affected is that coding for neurotensin (NT), a tridecapeptide that is heterogeneously distributed in the central nervous system of many mammals including humans, where it functions as a neurotransmitter or neuromodulator (6, 7). Several lines of evidence suggest that NT may play an important role in the etiology and͞or pharmacotherapy of schizophrenia and other neuropsychiatric disorders. NT regulates the dopaminergic neuronal systems, increasing the firing rate of nigrostriatal neurons as well as attenuating dopamine autoinhibition of nigrostriatal neurons. NT levels have been reported reduced in the cerebrospinal fluid of drug-free schizophrenic patients, but return to normal levels following haloperidol treatment (8).Previous studies have shown that 7 h following a single dose of haloperidol, a dramatic increase in NT mRNA occurs in neurons of the dorsolateral striatum (DLST) of the rat brain, a component of the basal ganglia circuitry that has been implicated in the regulation of motor output (9, 10). Haloperidol administration also leads to the induction of c-fos mRNA within 30 min in DL...

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A2 adenosine receptors: their presence and neuromodulatory role in the central nervous system

Cited by 79 publications

References 81 publications

Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons

Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons

Modulation of Adenylyl Cyclase Activity in Rat Striatal Homogenate by Dopaminergic Receptors

Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice

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