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Angiotensin converting enzyme in the Parkinsonian brain.

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Angiotensin Converting
Enzyme in the
Parkinsonian Brain
U. K. Rinne, M D , V. Koskinen, BSc, H. Iaaksonen, MD.
and 0. Tenovuo, MD
Angiotensin converting enzyme (ACE) is distributed unevenly throuRhout thc human brain. with higher conccntration in the corpus striaturn [4]. Arregui c t al [ I ] have recently described selective depletion of ACE in the corpus
striatum in Huntington's chorea. To examine further t h e
angicrtensin system in extrapyramidal disorders, we have
studied whether any alterations of brain ACE occur in Parkinson's disease, in which t h e most pronounced
ncuropatholcrgical changes arc located in the substantia
nigra-striatum system 1.21.
Postmortem brain samples were obtained from 2 women
and 4 men with Parkinson's disease. The mean age was 73
? 4 years, and the mean duration of the disease was 8 ? 1
years. T w o of the patients had k e n treated with levodopa
and benserazide but 4 patients only with anticholinergic
drugs. T h e mean interval benvt.cn death and autopsy was
26 2 12 hours. Various regions o f the brain (Table) were
dissected for biochemical analysis. Samples of cerebral cort c x were taken from rhe left frontal lobc.
Correspomiing control brain samples from 6 patients
aged 75 -C 6 years without extrapyramidal disordcrs were
wkco ar the same time as the parkinsonian postmortem
brains became available. T h e mc.m interval between death
and autopsy was 36 % 6 hours.
T h e tissucs were homogcnited in 0.1 M TrisFrom the Department of Neurology. Universiry of Turku. Turku.
Finland.
Accepted for publicatiaw Mar 28. 1978.
Address repriiit requests to Prof Kinne, Dcpitrtment o f Neurology. University of Turku, SF-20520 Turku 52. Finland.
hydrochloride huffer ( p H 7.40 at 57°C) and stored c k p
frozen until analyzed, a mcan lapse of 34 2 14 days. T h e
activity of ACE was determined by the method of Yang and
Neff IS]. Protein was determined by the method o f I.owry
et al [ 31 with hovine serum albumin as the standard.
Higher activity of ACE was fourid in the corpus striatum
in both the control and the parkinsonian patients (Table).
O n the other hand, ACE activity in the substmtia nigra was
less than that in the other cxtrapyrlimidal nuclci T h e m was
n o sex difference in the findings in either thc control or the
parkinsonian patients.
T h e activity o f ACE in all the brain regions studicJ did
not differ in patients with Parkinson's disease and in controls. Moreover. treatment with Ievodopa and benserazide
had no evident effect on ACE activity in the parkinsonian
brain (see the 'I'able).
T h e findings support the effect of selective depletion of
ACE ;ictivity in the corpus srriatum in Huntington's chorea
and provide further evidence of the occurrence of different
biochemical and pathological changes in thc extrapyramidal
systc'm of choreic and pdrkinsonian patients.
Supported by a grant from the Medical Research Council.
Acadcmy of Finland.
References
1. A r r c y i A, Bennett JP, Bird ED, ct al: Huntington's chorea:
sclcctive depletion of a< tivity of angiorensin tonvertinp cnzyme
the corpus striatum. Ann Neurol 2:294-208, 1077
2. Hcrnheimer H, Birkmayer W, Hornykiewicz 0. er al: Brain
dopamine :ind the syndromes of Parkinson and Huntington:
clinical, morphological and ncurochemicd correlarlcms. J
Ncurol Sci 20:415-455. 1973
3. Lowry O H , Koseborough NJ, Farr AL. et al: Protein mcasuremcnt alith thc Folin phenol rcagcnr. J Biol Chem 1 0 3 2652'5. 1951
4. Poth MM, Heach RG, Ward M: Angiotensin-converting enzyme in human brain. J Neurochem 25:83-85, 1075
5 . Y m g H-YT, Neff N H Distribution and properties of angiotcnsin converting mzyme o f rat brain. J Neurlxhem
19:2443-2450. 1972
in
Angiotensin Converting Enzyme Ac.ttvity in Brain K e g i o m o/ PdrkinJoniuti Palients and CmiirolJa
Group
Parkinsonian patients
Without 1evodop;i
With Ievodopa
Controls
No. o f
P.itients
Caudate
Nucleus
6
4
4.02
3.95
4.14
3.21
2
0
t
0.53
t
0.67
t
1.23
0.20
?
Putamcn
Pallidum
Su hstantia
Nigra
Cerc*hraI
Corrcs
3.22 + 0.35
3.36 -t 0.51
2.95 2 0.46
2.64 % 0.20
2.60 IT 0.35
2.82 _c 0.51
L.16? 0.10
2.29 ? 0.32
1.89 _c 0.49
1.87 2 0.64
1 . 0 5 2 1.04
1.75 2 0.29
0.32
0.34
0.30
0.35
%
0.09
-t
0.11
2
0.23
0.03
-t
aValues are in nanomolcs of His-Lcu per minute per milligram of protein, mean t S I M
Notes and Lettcrs
483
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angiotensins, enzymes, brain, converting, parkinsonism
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