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

Gasser, P.; Lowry, Christopher A.; Orchinik, Miles

doi:10.1523/jneurosci.0570-06.2006

Cited by 127 publications

(112 citation statements)

References 69 publications

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“…The density of each dot was quantified using ImageJ 1.38x. 1998; Gasser et al, 2006). The results of this study suggested a new role for OCT3, as a determinant of the sensitivity of treatment with oxaliplatin against colorectal cancer.…”

Section: Platinum Accumulation In Colorectal Cancer-derived Cell Linementioning

confidence: 68%

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Yokoo

Masuda²,

Yonezawa

et al. 2008

Drug Metab Dispos

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ABSTRACT:The effect of oxaliplatin against colorectal cancer is superior to that of cisplatin, but the molecular mechanism(s) involved is not clear. We found previously that oxaliplatin, but not cisplatin, was transported by human (h) and rat organic cation transporter 3 (OCT3)/SLC22A3. In the present study, we examined whether hOCT3 was significantly involved in the oxaliplatin-induced cytotoxicity and accumulation of platinum in colorectal cancer. The level of hOCT3 mRNA in the colon was 9.7-fold higher in cancerous than in normal tissues in six Japanese patients (P ‫؍‬ 0.0247). In human colorectal cancer-derived cell lines, the mRNA of hOCT3 was highly expressed compared with that of other organic cation transporters. The release of lactate dehydrogenase (LDH) and accumulation of platinum with oxaliplatin treatment were increased in SW480 cells transfected with hOCT3 cDNA compared with empty vector-transfected cells. T84 and SW837 cells, with high levels of hOCT3, released more LDH and accumulated more platinum after oxaliplatin treatment than low hOCT3-expressing cells such as SW480, HCT116, HT29, and Lovo. However, the amount of platinum accumulated after cisplatin treatment did not differ among these six cell lines. The levels of hOCT3 expression in colon and rectum were also higher in cancerous than in normal tissues in Caucasian patients as determined by dot blotting. In conclusion, the hOCT3-mediated uptake of oxaliplatin into the cancers was suggested to be important for its cytotoxicity, and hOCT3 expression may be a marker for cancer chemotherapy including oxaliplatin.

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Section: Platinum Accumulation In Colorectal Cancer-derived Cell Linementioning

confidence: 68%

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Yokoo

Masuda²,

Yonezawa

et al. 2008

Drug Metab Dispos

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“…The high-capacity, low-affinity OCT3 is thought to act as a secondary means of norepinephrine clearance, and is inhibited by physiological levels of corticosterone (Gasser et al, 2006). The extent to which BNST norepinephrine is taken up by OCTs in vivo is not currently known, however, NET knockout mice still demonstrate catecholamine clearance in brain slices (Xu et al, 2000) relative to dopamine transporter knockouts (Giros et al, 1996), indicating this may be a significant clearance mechanism for norepinephrine.…”

Section: Discussionmentioning

confidence: 99%

Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

Fox

Studebaker

Swofford

et al. 2015

Neuropsychopharmacol

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Previous work has demonstrated the importance of genetic factors and stress-sensitive circuits in the development of affective disorders. Anxiety and numerous psychological disorders are comorbid with substance abuse, and noradrenergic signaling in the bed nucleus of the stria terminalis (BNST) is thought to be a source of this convergence. Here, we examined the effects of different stressors on behavior and norepinephrine dynamics in the BNST of rat strains known to differ in their HPA-axis function. We compared the effects of acute morphine dependence and social isolation in non-anxious Sprague Dawley (SD) rats, and a depression model, Wistar-Kyoto (WKY) rats. We found a shared phenotype in drug-dependent and singly housed SD rats, characterized by slowed norepinephrine clearance, decreased autoreceptor function, and elevated anxiety. WKY rats exhibited changes in anxiety and autoreceptor function only following morphine dependence. To ascertain the influence of LC inhibition on this plasticity, we administered the LC-terminal-selective toxin DSP-4 to SD and WKY rats. DSP-4-treated SD rats demonstrated a dependence-like phenotype, whereas WKY rats were unchanged. Overall, our findings suggest that individuals with varying stress susceptibilities have different noradrenergic signaling changes in response to stress. These changes may establish conditions that favor stress-induced reinstatement and increase the risk for addiction.

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“…5-HT has been associated with stress in response to aversive stimuli in a number of brain regions, and biochemical interactions occur at multiple levels between the 5-HTergic and glucocorticoid systems (Gasser et al, 2006;Lanfumey et al, 2008;Linthorst and Reul, 2007). Of the stimuli we presented, the two that did evoke significant increases in extracellular IC 5-HT were both potentially stressful.…”

Section: -Ht Fluctuations During Environmental Eventsmentioning

confidence: 99%

Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

Hall

Rebec

Hurley

2010

Journal of Experimental Biology

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SUMMARYNeuromodulation by serotonin (5-HT) could link behavioral state and environmental events with sensory processing. Within the auditory system, the presence of 5-HT alters the activity of neurons in the inferior colliculus (IC), but the conditions that influence 5-HT neurotransmission in this region of the brain are unknown. We used in vivo voltammetry to measure extracellular 5-HT in the IC of behaving mice to address this issue. Extracellular 5-HT increased with the recovery from anesthesia, suggesting that the neuromodulation of auditory processing is correlated with the level of behavioral arousal. Awake mice were further exposed to auditory (broadband noise), visual (light) or olfactory (2,5-dihydro-2,4,5-trimethylthiazoline, TMT) stimuli, presented with food or confined in a small arena. Only the auditory stimulus or restricted movement increased the concentration of extracellular 5-HT in the IC. Changes occurred within minutes of stimulus onset, with the auditory stimulus increasing extracellular 5-HT by an average of 5% and restricted movement increasing it by an average of 14%. These findings suggest that the neuromodulation of auditory processing by 5-HT is a dynamic process that is dependent on internal state and behavioral conditions.

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

Cited by 127 publications

References 69 publications

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli

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