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Journal of Neuroscience, Vol 4, 111-124, Copyright © 1984 by Society for Neuroscience
DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization
CC Ouimet, PE Miller, HC Hemmings Jr, SI Walaas and P Greengard
Immunocytochemical studies have been carried out to determine the regional
and cellular distribution of DARPP-32, a protein the phosphorylation of
which can be regulated by dopamine and cAMP in intact cells. These
immunocytochemical studies indicate tha DARPP-32 is localized primarily in
those brain regions enriched in dopaminergic nerve terminals. Moreover, the
staining pattern supports the conclusion that the DARPP-32 is present in
dopaminoceptive neurons, i.e., neurons that receive a dopamine input, and
that it is absent from the dopaminergic neurons themselves. Within the
caudatoputamen, nucleus accumbens, olfactory tubercle, bed nucleus of the
stria terminalis, and portions of the amygdaloid complex, all of which
receive a strong dopamine input, DARPP-32 immunoreactivity is present in
neuronal cell bodies and dendrites. In brain regions that are known to
receive projections from these nuclei, puncta (presumed nerve terminals)
are strongly immunoreactive for DARPP-32 but indigenous cell bodies and
dendrites are not immunoreactive. These target areas include the globus
pallidus, ventral pallidum, entopeduncular nucleus, and the pars reticulata
of the substantia nigra. No immunoreactivity is detected in neuronal cell
bodies or dendrites in any of the dopaminergic nuclei. Furthermore, nerve
terminals immunoreactive for DARPP-32 do not resemble dopaminergic
varicosities in either their morphology or their pattern of distribution.
Many neurons are weakly immunoreactive for DARPP-32 and some of these are
found in areas that apparently lack a dopaminergic input: weakly labeled
neuronal cell bodies and dendrites were found throughout the neocortex,
primarily in layer VI, and in the Purkinje neurons of the cerebellum.
DARPP-32 immunoreactivity is also present in certain glial cells,
especially in the median eminence, arcuate nucleus, and medial habenula.
The present immunocytochemical studies, taken together with biochemical
studies (Hemmings, H.C., Jr., A.C. Nairn, D.W. Aswad, and P. Greengard
(1984) J. Neurosci. 4: 99-110; Walaas, S.I., and P. Greengard (1984) J.
Neurosci. 4: 84-98) on DARPP- 32, indicate that DARPP-32, is present in the
subclass of dopaminoceptive neurons containing D-1 receptors (dopamine
receptors coupled to adenylate cyclase). DARPP-32 may be an effective
marker for certain of the actions of dopamine that are mediated through
cAMP and its associated protein kinase.
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