[3H]Desipramine Binding to Rat Brain Tissue: Binding to Both Noradrenaline Uptake Sites and Sites Not Related to Noradrenaline Neurons

Bäckström, Inger T.; Ross, Svante B.; Marcusson, Jan

doi:10.1111/j.1471-4159.1989.tb01853.x

Cited by 30 publications

(11 citation statements)

References 21 publications

(18 reference statements)

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“…This suggests that the high-affinity [3H]desipraminebinding site represents binding to the noradrenaline up take site. However, in comparison with the rat brain [11], the Kj values for noradrenaline and its uptake inhibitors were 100-1,000 times higher in the present study of the human brain. Moreover, the Kj value for noradrenaline inhibition of [3H]desipramine binding in the present study was 1,500 times higher than the Km value for the noradrenaline uptake process in human brain tissue reported by Haberland and Hetey [17].…”

Section: Discussionmentioning

confidence: 57%

“…The tissue preparation was carried out as previously described for the rat brain [11]. The brain tissues were homogenized in 20 ml ice-cold assay buffer (50 m,W Tris-HCl, 120 r\M NaCI, 5 m.V/ K.CI, pH 7.4) using a Kinematica polytron homogenizer at setting 4 for 10 s. The homogenates were centrifuged (48,000 g. 10 min) and then homogenized again.…”

Section: Ishjdesipramine Bindingmentioning

confidence: 99%

“…However, heterogeneity of the binding has also been discussed and [3H]desipramine appears to bind to both high-and low-affinity sites in the rat brain [11,12]. The high-affinity portion is related to the noradrenaline uptake mechanism [11], In a study on human brain tis sue, the [3H]desipramine binding appeared to be homo geneous in nature [13]. Regarding the heterogeneity of the binding in the rat brain, we wanted to reinvestigate and focus on the pharmacological characteristics of [3H]desipramine binding in the human brain.…”

Section: Introductionmentioning

confidence: 99%

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High- and Low-Affinity [3H]Desipramine-Binding Sites in Human Postmortem Brain Tissue

Bäckström¹,

Marcusson²

1990

Neuropsychobiology

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The binding of [³H]desipramine to human brain tissue was characterized. Competition studies in the frontal cortex and hypothalamus revealed a single-site binding model for noradrenaline (K_i 120–190 μM). The noradrenaline uptake inhibitors nisoxetine, nortriptyline and desipramine fitted two-site binding models and these compounds exhibited 10–80 times lower K_i values than the serotonin uptake inhibitor citalopram. The high-affinity component of the nisoxetine-sensitive [³H]desipramine binding (K_i 50–110 nM) approximated the binding sensitive to noradrenaline. This binding fraction was defined as that sensitive to 1 μM nisoxetine and showed a maximum binding capacity (B_max) of 380 ± 80 fmol/mg protein and an apparent K_d of 5.1 (4.5–5.7) nM in the hypothalamus. The binding was also investigated in 25 additional brain regions without finding detectable amounts of binding. However, when the specific binding was defined as that sensitive to 100 μM nisoxetine, low-affinity binding where B_max and K_d were not possible to determine was obtained in all brain regions investigated. It is concluded that [³H]desipramine binding to human brain tissue represents multiple binding sites. Only when regarding binding sensitive to noradrenaline and to the high-affinity component of noradrenaline uptake inhibitors is the binding saturable and of high affinity. It is possible that this site represents the uptake site for noradrenaline.

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Section: Discussionmentioning

confidence: 57%

Section: Ishjdesipramine Bindingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High- and Low-Affinity [3H]Desipramine-Binding Sites in Human Postmortem Brain Tissue

Bäckström¹,

Marcusson²

1990

Neuropsychobiology

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“…In this study, we used [ 3 H]nisoxetine to determine the distribution of NETs within the human locus coeruleus and dorsal raphe. [ 3 H]nisoxetine has a high affinity for NETs (Tejani-Butt et al, 1990;TejaniButt, 1992;Tejani-Butt and Ordway, 1992) and does not possess the complications of other ligands used for analysis of NETs, i.e., binding to intracellular nonadrenergic sites (Laduron et al, 1982;Backstrom et al, 1989; Backstrom and Marcusson, 1990). …”

Section: Abstract: Norepinephrine Transporters; Norepinephrine Uptakmentioning

confidence: 99%

“…3 H]desipramine binds with high affinity to NETs, it also binds to intracellular nonadrenergic sites (Laduron et al, 1982;Backstrom et al, 1989;Backstrom and Marcusson, 1990), making interpretation of binding results difficult. [ 3 H]mazindol binds with high affinity to NETs but also binds to dopamine transporters so that nonspecific binding must be measured by careful choice of a displacing ligand and its concentration (Donnan et al, 1991).…”

Section: Although [mentioning

confidence: 99%

Pharmacology and Distribution of Norepinephrine Transporters in the Human Locus Coeruleus and Raphe Nuclei

et al. 1997

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The norepinephrine transporter (NET ) is a site of action for tricyclic antidepressant drugs and for drugs of abuse such as amphetamine and cocaine. In this study, the binding of [ 3 H]nisoxetine to NETs in the noradrenergic cell group, the locus coeruleus, and the serotonergic cell groups, the dorsal raphe nuclei, was measured autoradiographically in postmortem human brain. 3 H]nisoxetine binding to NETs in monoaminergic nuclei was assessed by measuring the inhibition of its binding by desipramine, imipramine, or citalopram. The order of affinities of these drugs was identical in the locus coeruleus and dorsal and median raphe and was characteristic of binding to NETs (desipramine Ͼ imipramine Ͼ citalopram). Thus, high levels of NETs and an uneven distribution of NETs occur in the locus coeruleus as well as in the dorsal raphe nuclei of the human.

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The comparative distributions of the monoamine transporters in the rodent, monkey, and human amygdala

Smith

Porrino

2008

Brain Struct Funct

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The monoamines in the amygdala modulate multiple aspects of emotional processing in the mammalian brain, and organic or pharmacological dysregulation of these systems can result in affective pathologies. Knowledge of the normal distribution of these neurotransmitters, therefore, is central to our understanding of both the normal processes regulated by the amygdala and the pathological conditions associated with monoaminergic dysregulation. The monoaminergic transporters have proven to be accurate and reliable markers of the distributions of their substrates. The purpose of this review was twofold: First, to briefly recount the functional relevance of dopamine, serotonin, and norepinephrine transmission in the amygdala, and second, to describe and compare the distributions of the monoamine transporters in the rodent, monkey, and human brain. The transporters were found to be heterogeneously distributed in the amygdala. The dopamine transporter (DAT) is consistently found to be extremely sparsely distributed, however the various accounts of its subregional topography are inconsistent, making any cross-species comparisons difficult. The serotonin transporter (SERT) had the greatest overall degree of labeling of the three markers, and was characterized by substantial inter-species variability in its relative distribution. The norepinephrine transporter (NET) was shown to possess an intermediate level of labeling, and like the SERT, its distribution is not consistent across the three species. The results of these comparisons indicate that caution should be exercised when using animal models to investigate the complex processes modulated by the monoamines in the amygdala, as their relative contributions to these functions may differ across species.

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[³H]Desipramine Binding to Rat Brain Tissue: Binding to Both Noradrenaline Uptake Sites and Sites Not Related to Noradrenaline Neurons

Cited by 30 publications

References 21 publications

High- and Low-Affinity [<sup>3</sup>H]Desipramine-Binding Sites in Human Postmortem Brain Tissue

High- and Low-Affinity [<sup>3</sup>H]Desipramine-Binding Sites in Human Postmortem Brain Tissue

Pharmacology and Distribution of Norepinephrine Transporters in the Human Locus Coeruleus and Raphe Nuclei

The comparative distributions of the monoamine transporters in the rodent, monkey, and human amygdala

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