Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

Shi, Dan; Nikodijevic, Olga; Jacobson, Kenneth A.; Daly, John W.

doi:10.1007/bf00733753

Cited by 145 publications

(98 citation statements)

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“…In vitro and in vivo studies (Lupica et al, 1991;Abbracchio et al, 1992;Shi et al, 1993;Adami et al, 1995) indicate that chronic exposure of adenosine A 2A receptors to agonists or antagonists does not result in changes of either receptor density or their dissociation constants. Moreover, contrary to a drastic reversal of effect reported by us in cases where adenosine A 1 and A 3 receptors were stimulated either acutely or chronically (Von Lubitz et al, 1994a,b,c), chronic exposure to either an agonist or antagonist of the A 2 receptor results in a much blunted response reversal.…”

Section: Discussionmentioning

confidence: 99%

Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist

Lubitz¹,

Lin

Jacobson³

1995

European Journal of Pharmacology

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132

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Despite significant progress in understanding of the potential of adenosine A 1 receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A 2A receptors on the outcome of a cerebrovascular arrest. In view of a major role played by adenosine A 2 receptors in the regulation of cerebral blood flow, we have investigated the effect of both acute and chronic administration of the selective adenosine receptor agonist 2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5′-Nethylcarboxoamidoadenosine (APEC) and antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in gerbils. Acute treatment with APEC improved recovery of postischemic blood flow and survival without affecting neuronal preservation in the hippocampus. Acute treatment with CSC had no effect on the cerebral blood flow but resulted in a very significant protection of hippocampal neurons. Significant improvement of survival was present during the initial 10 days postischemia. Due to subsequent deaths of animals treated acutely with CSC, the end-point mortality (14 days postischemia) in this group did not differ statistically from that seen in the controls. It is, however, possible that the late mortality in the acute CSC group was caused by the systemic effects of brain ischemia that are not subject to the treatment with this drug. Chronic treatment with APEC resulted in a statistically significant improvement in all studied measures. Although chronic treatment with CSC improved postischemic blood flow, its effect on neuronal preservation was minimal and statistically insignificant. Mortality remained unaffected. The results indicate that the acute treatment with adenosine A 2A receptor antagonists may have a limited value in treatment of global ischemia. However, since administered CSC has no effect on the reestablishment of postischemic blood flow, treatment of stroke with adenosine A 2A receptor antagonists may not be advisable. Additional studies are necessary to elucidate whether chronically administered drugs acting at adenosine A 2 receptors may be useful in treatment of stroke and other neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist

Lubitz¹,

Lin

Jacobson³

1995

European Journal of Pharmacology

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132

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“…From the above studies, upregulation of the A1AR and/or A1AR activation would be a highly desirable therapeutic strategy; hence, we examined the effects of caffeine and/or ADAC on MOG-induced EAE because chronic caffeine treatment upregulates A1AR expression in the CNS (Shi et al, 1993) and A1AR activation after caffeine treatment might synergistically reduce EAE severity. After the induction of EAE in A1AR ϩ/ϩ mice, A1AR immunoreactivity on macrophage/microglia in spinal cord was reduced (Fig.…”

Section: A1armentioning

confidence: 99%

A1 Adenosine Receptor Upregulation and Activation Attenuates Neuroinflammation and Demyelination in a Model of Multiple Sclerosis

Tsutsui¹,

Schnermann²,

Noorbakhsh³

et al. 2004

J. Neurosci.

299

265

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The neuromodulator adenosine regulates immune activation and neuronal survival through specific G-protein-coupled receptors expressed on macrophages and neurons, including the A1 adenosine receptor (A1AR). Here we show that A1AR null (A1AR Ϫ/Ϫ ) mice developed a severe progressive-relapsing form of experimental allergic encephalomyelitis (EAE) compared with their wild-type (A1AR ϩ/ϩ ) littermates. Worsened demyelination, axonal injury, and enhanced activation of microglia/macrophages were observed in A1AR Ϫ/Ϫ animals. In addition, spinal cords from A1AR Ϫ/Ϫ mice demonstrated increased proinflammatory gene expression during EAE, whereas anti-inflammatory genes were suppressed compared with A1AR ϩ/ϩ animals. Macrophages from A1AR Ϫ/Ϫ animals exhibited increased expression of the proinflammatory genes, interleukin-1␤, and matrix metalloproteinase-12 on immune activation when matched with A1AR ϩ/ϩ control cells. A1AR Ϫ/Ϫ macrophage-derived soluble factors caused significant oligodendrocyte cytotoxicity compared with wild-type controls. The A1AR was downregulated in microglia in A1AR ϩ/ϩ mice during EAE accompanied by neuroinflammation, which recapitulated findings in multiple sclerosis (MS) patients. Caffeine treatment augmented A1AR expression on microglia, with ensuing reduction of EAE severity, which was further enhanced by concomitant treatment with the A1AR agonist, adenosine amine congener. Thus, modulation of neuroinflammation by the A1AR represents a novel mechanism that provides new therapeutic opportunities for MS and other demyelinating diseases.

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“…There is also a decreased susceptibility to seizures and ischemic brain damage (Georgiev et al, 1993;Bona et al, 1995). Several studies have shown that chronic treatment with caffeine causes an upregulation of adenosine A, receptors (Fredholm, 1982;Johansson et al, 1993a;Shi et al, 1993). There is also evidence that receptors for other transmitters, especially GABA and ACh, as well as G,-proteins are affected (Ramkumar et al, 1988;Shi et al, 1993).…”

Section: Gaba Releasementioning

confidence: 99%

“…Several studies have shown that chronic treatment with caffeine causes an upregulation of adenosine A, receptors (Fredholm, 1982;Johansson et al, 1993a;Shi et al, 1993). There is also evidence that receptors for other transmitters, especially GABA and ACh, as well as G,-proteins are affected (Ramkumar et al, 1988;Shi et al, 1993). Interestingly, both NGFI-A and NGFI-B proteins can bind specifically to DNA (Christy and Nathans, 1989;Wilson et al, 1991) and act as transcription factors.…”

Section: Gaba Releasementioning

confidence: 99%

Biphasic changes in locomotor behavior and in expression of mRNA for NGFI-A and NGFI-B in rat striatum following acute caffeine administration

1995

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The time course of expression of mRNA for NGFI-A and NGFI-B after a single intraperitoneal injection of saline or caffeine was examined using in situ hybridization. Administration of a high dose of caffeine (100 mg/kg) decreased locomotor behavior and increased NGFI-A and NGFI- B mRNA in the entire striatum. A lower dose of caffeine (50 mg/kg) caused a weak enhancement of both messages, which was confined to the lateral part of caudate-putamen. This dose increased horizontal, but not vertical, movement. In rats treated with the lowest dose of caffeine (25 mg/kg), the expression of both investigated genes tended to be lower than for saline-treated rats and both horizontal and vertical locomotor activity increased markedly. The reduction in the number of labeled neurons seemed to occur predominantly in enkephalin- containing neurons, which coexpress adenosine A2A receptors and dopamine D2 receptors. The decrease of mRNA for NGFI-A, NGFI-B, and jun B caused by caffeine (25 mg/kg) could be mimicked by the D2 agonist quinpirole (1 and 3 mg/kg). Moreover, caffeine could significantly decrease the expression seen following treatment with the D2 antagonist raclopride (2 mg/kg). In addition, in the parietal cortex, 25 mg/kg of caffeine caused a significant elevation of both examined immediate early genes. Thus, biphasic changes in locomotion induced by caffeine are paralleled by biphasic changes in mRNA for NGFI-A, NGFI-B, and jun B. The results also provide additional support for a functionally important interaction between adenosine and dopamine D2 receptors.

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Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

Cited by 145 publications

References 50 publications

Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist

Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist

A1 Adenosine Receptor Upregulation and Activation Attenuates Neuroinflammation and Demyelination in a Model of Multiple Sclerosis

Biphasic changes in locomotor behavior and in expression of mRNA for NGFI-A and NGFI-B in rat striatum following acute caffeine administration

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