Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia.
In the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine-containing cell bodies. In contrast, angiotensin-converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin-converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin-converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system.
Allen
A M
AM
University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
MacGregor
D P
DP
Chai
S Y
SY
Donnan
G A
GA
Kaczmarczyk
S
S
Richardson
K
K
Kalnins
R
R
Ireton
J
J
Mendelsohn
F A
FA
D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D011699:Putamen / Q000378:metabolism* / Q000473:pathology; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
D011945:Receptors, Angiotensin; D000804:Angiotensin II; C009210:sarleucin; D004298:Dopamine