Pharmacological characterization of dopamine transport in cultured rat astrocytes

Inazu, Masato; Kubota, Nobuo; Takeda, Hiroshi; Zhang, Jun; Kiuchi, Yuji; Oguchi, Katsuji; Matsumiya, Teruhiko

doi:10.1016/s0024-3205(99)00175-7

Cited by 52 publications

(42 citation statements)

References 18 publications

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“…We found OCT3-like immunoreactivity in presumed glial and ependymal cells in the DMH. This agrees with previous reports of OCT3 expression in cultured astrocytes (Russ et al, 1996;Schomig et al, 1998;Inazu et al, 1999Inazu et al, , 2003a and in ependymal cells in rat circumventricular organs (Vialou et al, 2004) and suggests that OCT3 activity in either or both of these cell types may have mediated the effects observed in our functional assays and may play roles in monoamine clearance in the DMH. Glial and ependymal cells also express other mediators of monoamine clearance and metabolism, including SERT (Inazu et al, 2001;Verleysdonk et al, 2004) and monoamine oxidase (MAO) (Ekblom et al, 1993;Verleysdonk et al, 2004).…”

Section: Discussionsupporting

confidence: 93%

Corticosterone-Sensitive Monoamine Transport in the Rat Dorsomedial Hypothalamus: Potential Role for Organic Cation Transporter 3 in Stress-Induced Modulation of Monoaminergic Neurotransmission

Gasser¹,

Lowry²,

Orchinik³

2006

J. Neurosci.

127

104

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Section: Discussionsupporting

confidence: 93%

Corticosterone-Sensitive Monoamine Transport in the Rat Dorsomedial Hypothalamus: Potential Role for Organic Cation Transporter 3 in Stress-Induced Modulation of Monoaminergic Neurotransmission

Gasser¹,

Lowry²,

Orchinik³

2006

J. Neurosci.

127

104

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“…WT and PK-KO mice midbrain astrocytes lack high-affinity [ 3 H]DA uptake (at 19 and 38 nM DA concentration, 37°C incubation for 20 min, and for blank blocked by DA transporter inhibitor at nanomolar concentration, even at 10 and 15 M). In rat cortical astroglia, DA transport is mediated by norepinephrine transport (Inazu et al, 1999;Takeda et al, 2002). However, astrocytes play a role in the clearance of DA from the extracellular space, when DA is at micromolar concentration (Karakaya et al, 2007), and, of course, astrocytes play a very important role in the DA metabolism by monoamine oxidase B (MAO-B).…”

Section: Effects Of Wt and Pk-ko Glia-conditioned Medium On Fetal Midmentioning

confidence: 99%

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Solano¹,

Casarejos²,

et al. 2008

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Parkin mutations in humans produce parkinsonism whose pathogenesis is related to impaired protein degradation, increased free radicals, and abnormal neurotransmitter release. The role of glia in parkin deficiency is little known. We cultured midbrain glia from wild-type (WT) and parkin knock-out (PK-KO) mice. After 18 -20 d in vitro, PK-KO glial cultures had less astrocytes, more microglia, reduced proliferation, and increased proapoptotic protein expression.PK-KO glia had greater levels of intracellular glutathione (GSH), increased mRNA expression of the GSH-synthesizing enzyme ␥-glutamylcysteine synthetase, and greater glutathione S-transferase and lower glutathione peroxidase activities than WT. The reverse happened in glia cultured in serum-free defined medium (EF12) or in old cultures. PK-KO glia was more susceptible than WT to transference to EF12 or neurotoxins (1-methyl-4-phenylpyridinium, blockers of GSH synthesis or catalase, inhibitors of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3 kinases), aging of the culture, or combination of these insults. PK-KO glia was less susceptible than WT to Fe 2ϩ plus H 2 O 2 and less responsive to protection by deferoxamine. Old WT glia increased the expression of heat shock protein 70, but PK-KO did not. Glia conditioned medium (GCM) from PK-KO was less neuroprotective and had lower levels of GSH than WT. GCM from WT increased the levels of dopamine markers in midbrain neuronal cultures transferred to EF12 more efficiently than GCM from PK-KO, and the difference was corrected by supplementation with GSH. PK-KO-GCM was a less powerful suppressor of apoptosis and microglia in neuronal cultures. Our data prove that abnormal glial function is critical in parkin mutations, and its role increases with aging.

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“…The astroglial cells accumulate monoamines and show different affinity to each of them (Hansson 1985). Astrocytes express the extraneuronal monoamine transporter system, which is involved in the activation of centrally released dopamine (Inazu et al 1999). Hence, damaged neurons and neuroglial cells can alter brain amine levels considerably.…”

Section: Figmentioning

confidence: 99%

Hippocampal brain amines in methotrexate-induced learning and memory deficit

Madhyastha¹,

Somayaji²,

Rao³

et al. 2002

Can. J. Physiol. Pharmacol.

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Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

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Pharmacological characterization of dopamine transport in cultured rat astrocytes

Cited by 52 publications

References 18 publications

Corticosterone-Sensitive Monoamine Transport in the Rat Dorsomedial Hypothalamus: Potential Role for Organic Cation Transporter 3 in Stress-Induced Modulation of Monoaminergic Neurotransmission

Corticosterone-Sensitive Monoamine Transport in the Rat Dorsomedial Hypothalamus: Potential Role for Organic Cation Transporter 3 in Stress-Induced Modulation of Monoaminergic Neurotransmission

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Hippocampal brain amines in methotrexate-induced learning and memory deficit

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