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I2-imidazoline binding sites and monoamine oxidase activity in human postmortem brain from patients with Parkinson's
C Gargalidis-Moudanos1, N Pizzinat, F Javoy-Agid
1INSERM U388, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
Abstract:
I2-imidazoline binding site (I2BS) has been identified with a regulatory site located on a sub-population of monoamine oxidase (MAO)-A and -B. Previous studies showed a modification of MAO and I2BS in the elderly and in neurodegenerative processes such as Alzheimer's disease. In the present study, we studied the potential modification of I2 binding sites and monoamine oxidases in Parkinson's disease. Putamen and cerebral cortex were collected from 17 normal subjects (79 +/- 12 yr) and 16 patients (76 +/- 9 yr) affected by Parkinson's disease. In mitochondrial preparations, radioligand binding studies with [3H]idazoxan showed that putamen and frontal cortex express equivalent amount of I2BS. The density and affinity of I2BS were similar in normal subjects (putamen: Bmax = 207 +/- 58 fmol/mg of protein, Kd = 10.1 +/- 3.4 nM; cerebral cortex: Bmax = 193 +/- 54 fmol/mg of protein, Kd = 12.8 +/- 6.8 nM) and Parkinson's disease patients (putamen: Bmax = 193 +/- 60 fmol/mg of protein, Kd = 9.8 +/- 4.6 nM; cerebral cortex: Bmax = 199 +/- 49 fmol/mg of protein, Kd = 15.9 +/- 8.1 nM). The activity of total monoamine oxidase and monoamine oxidase B, measured by [14C]tyramine and [14C]phenylethylamine oxidation, respectively, were higher in putamen than in cerebral cortex. No differences have been detected in the enzyme activity between normal and pathological subjects. These data suggest that, although MAO and I2BS may play a role in the development of Parkinson's disease, they are not altered in the chronic phase of this disease.
Insights
Monoamine oxidase (MAO) and I2-imidazoline binding sites (I2BS) are not altered in chronic Parkinson's disease. While MAO and I2BS may influence Parkinson's development, this study found no significant changes in affected patients.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- The I2-imidazoline binding site (I2BS) is a regulatory site on monoamine oxidase (MAO)-A and -B.
- Previous research indicates MAO and I2BS alterations in aging and neurodegenerative diseases like Alzheimer's.
Purpose of the Study:
- To investigate potential modifications of I2 binding sites and monoamine oxidases in Parkinson's disease.
Main Methods:
- Radioligand binding studies using [3H]idazoxan to assess I2BS density and affinity.
- Enzyme activity assays measuring [14C]tyramine and [14C]phenylethylamine oxidation for total MAO and MAO-B activity.
- Analysis of putamen and cerebral cortex tissue from normal subjects and Parkinson's disease patients.
Main Results:
- I2BS density and affinity were similar in both normal subjects and Parkinson's disease patients across putamen and cerebral cortex.
- MAO and MAO-B enzyme activity was higher in the putamen compared to the cerebral cortex in both groups.
- No significant differences in MAO or MAO-B activity were found between normal and Parkinson's disease subjects.
Conclusions:
- The study suggests that MAO and I2BS are not altered in the chronic phase of Parkinson's disease.
- Despite potential roles in disease development, these targets do not show significant changes in established Parkinson's disease.