| 1. |
- Allard, Per, et al.
(författare)
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Dopamine uptake sites in Parkinson's disease and in dementia of the Alzheimer type.
- 1994
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 637:1-2, s. 262-6
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Tidskriftsartikel (refereegranskat)abstract
- The binding of [3H]GBR-12935 to dopamine (DA) uptake sites was studied in post-mortem putamen from a control group and from patients with Parkinson's disease (PD) or dementia of the Alzheimer type (DAT). The specific binding (Bmax) was almost completely abolished in the PD group and reduced by 65% in the DAT group. There were no significant differences in apparent binding affinity (Kd) between the DAT group and controls. The decreases in [3H]GBR-12935 binding to DA uptake sites in this study indicate a marked degeneration of DA neurites in the putamen in PD and also in DAT.
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| 2. |
- Allard, Per, et al.
(författare)
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[3H]GBR-12935 binding to cytochrome P450 in the human brain.
- 1994
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Ingår i: Journal of Neurochemistry. - 0022-3042 .- 1471-4159. ; 62:1, s. 342-8
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Tidskriftsartikel (refereegranskat)abstract
- The presence of multiple [3H]GBR-12935 binding sites in the human brain has been revealed in several recent studies. One site represents the dopamine uptake site. In rat brain it was demonstrated that [3H]GBR-12935 also binds to nondopaminergic "piperazine acceptor sites." One of these sites has been identified as cytochrome P450IID1 in canine brain. [3H]GBR-12935 binding to the piperazine acceptor sites in the human brain was investigated in the present study. A pharmacological definition of the piperazine acceptor sites is presented: the [3H]GBR-12935 binding fraction that could be discriminated by 10 microM GBR-12909 in the presence of 0.3 microM mazindol. This binding fraction was saturable, with binding affinity in the range of 3-8 nM. It was also demonstrated that the piperazine acceptor or cytochrome P450-sensitive drugs cis-flupentixol and proadifen (SKF 525 A) compete for the same binding sites, suggesting the cytochrome P450 nature of the binding. The findings presented support the proposal that at least part of this fraction represents cytochrome P450IID6, the human form of P450IID1. The distribution of [3H]GBR-12935 binding to the suggested P450IID6-site in 12 brain regions was examined, without significant differences in binding densities between the regions. The significance of the present findings on the cytochrome P450 system in brain is discussed.
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| 3. |
- Allard, Per, et al.
(författare)
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[3H]GBR-12935 binding to dopamine uptake sites in rat striatum.
- 1990
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Ingår i: Neuropsychobiology. - 0302-282X .- 1423-0224. ; 23:4, s. 177-81
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the selective dopamine uptake inhibitor [3H]GBR-12935 to rat striatum was studied. Competition by mazindol and dopamine against [3H]GBR-12935 binding revealed monophasic binding curves. The addition of 100 microM dopamine to the mazindol competition inhibited only 80% of the binding, indicating more than one [3H]GBR-12935 binding site in rat striatum. When a binding fraction that could be discriminated by 1 microM mazindol or 1 mM dopamine was defined as specific binding, a single site binding model was obtained. The [3H]GBR-12935 binding was of protein nature, since it was abolished after protease treatment. Drug inhibition studies with the addition of low concentrations of mazindol and dopamine resulted in alterations in apparent Kd values only, suggesting competitive inhibition by these compounds against [3H]GBR-12935 binding. It is concluded that the [3H]GBR-12935 binding to rat striatum discriminated by 1 microM mazindol reflects binding to the substrate recognition site for the dopamine uptake.
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| 4. |
- Allard, Per, et al.
(författare)
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[3H]GBR-12935 binding to human cerebral cortex is not to dopamine uptake sites.
- 1994
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Ingår i: Journal of Neurochemistry. - 0022-3042 .- 1471-4159. ; 62:1, s. 338-41
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the dopamine uptake inhibitor [3H]GBR-12935 to 16 regions of the human brain was investigated in competition experiments with increasing concentrations of GBR-12909, mazindol, and dopamine. The methodology used included a relatively high tissue concentration (8 mg/ml) and addition of 5 mM KCl in the assay buffer. GBR-12909 inhibited 80-90% of the binding in most regions, whereas dopamine only inhibited the binding in the striatum. Mazindol inhibited only part of the cortical binding at concentrations of > 1 microM, whereas the inhibition in the caudate and the putamen also contained a high-affinity component representing the dopamine uptake site. It is concluded that the [3H]GBR-12935 binding sensitive to GBR-12909 cannot be regarded as specific binding to the dopamine uptake site because the displaceable binding most likely is not related to the dopamine uptake site.
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| 5. |
- Allard, Per, et al.
(författare)
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Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.
- 1990
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Ingår i: European Neurology. - 0014-3022 .- 1421-9913. ; 30:4, s. 181-5
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.
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| 6. |
- Allard, Per, et al.
(författare)
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Unaltered [3H]GBR-12935 binding after chronic treatment with dopamine active drugs.
- 1990
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Ingår i: Psychopharmacology. - 0033-3158 .- 1432-2072. ; 102:3, s. 291-4
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Tidskriftsartikel (refereegranskat)abstract
- Rats were injected intraperitoneally with haloperidol 0.5 mg/kg, raclopride 1 mg/kg, bromocriptine 2.5 mg/kg, d-amphetamine 2.5 mg/kg, or cocaine 10 mg/kg twice daily for 21 days. The animals were sacrificed 72 h after last injection. Control rats were injected with saline, following the same schedule. The radioligand [3H]GBR-12935 was used as a presynaptic marker for dopamine neurites. There were no significant differences in [3H]GBR-12935 binding to striatum between drug-treated rats and controls.
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| 7. |
- Leander, Peter, et al.
(författare)
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Early effect of gadopentetate and iodinated contrast media on rabbit kidneys
- 1992
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Ingår i: Investigative Radiology. - 0020-9996. ; 27:11, s. 922-926
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE AND OBJECTIVES. The authors compared the physiologic and nephrotoxic effects of the magnetic resonance imaging contrast medium gadopentetate with two conventional radiographic contrast media. METHODS. Rabbits were injected intravenously with one of the following solutions: 1) gadopentetate (0.1 M); 2) iohexol (300 mg I/mL); 3) metrizoate (300 mg I/mL); and 4) NaCl (0.9%). Blood samples were taken before and 5, 15, 45, 90, and 180 minutes after injection of the solutions and were analyzed for creatinine, aldosterone, and contrast media levels. Urine was sampled before and 1, 2.5, and 5 hours after injection of the solutions, and creatinine, leucine amino peptidase (LAP), alkaline phosphatase (ALP), gamma glutaryl transferase (GGT), and N-acetyl beta-D-glucosaminidase (NAG) activities were quantified. RESULTS. Contrast media clearance was similar for gadopentetate, iohexol, and metrizoate. Plasma aldosterone was significantly higher in the two groups injected with iodinated contrast agents compared with the gadopentetate and saline groups in the 3-hour samples. During the 5 hours after injection, the excretion of brushborder enzymes LAP, ALP, and gamma GT was significantly higher for all contrast media compared with pre-contrast values and 0.9% NaCl controls. NAG, a lysosomal enzyme from tubular cells, showed a significant increase compared with pre-contrast values for all contrast media. CONCLUSIONS. Intravenous injection of gadopentetate in rabbits showed nephrotoxicity of the same order as that of conventional iodinated contrast media.
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