Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [³H]captopril: Localization to a striatonigral pathway

We have visualized angiotensin-converting enzyme (ACE; dipeptidyl carboxypeptidase, peptidylpeptide hydrolase, EC 3.4.15.1) in rat brain by in vitro [³H]captopril autoradiography. [³H]captopril binding to brain slices displays a high affinity (K(d) = 1.8 x 10^-9 M) and a pharmacological profile similar to that of ACE activity. Very high densities of [³H]captopril binding were found in the choroid plexus and the subfornical organ. High densities were present in the caudate putamen and substantia nigra, zona reticulata. Moderate levels were found in the entopeduncular nucleus, globus pallidus, and median eminence of the hypothalamus. Lower levels were detectable in the supraoptic and paraventricular nuclei of the hypothalamus, the medial habenula, the median preoptic area, and the locus coeruleus. Injection of ibotenic acid or colchicine into the caudate putamen decreased [³H]captopril-associated autoradiographic grains by 85% in the ipsilateral caudate putamen and by > 50% in the ipsilateral substantia nigra. Thus, ACE in the substantia nigra is located on presynaptic terminals of axons originating from the caudate putamen, and ACE in the caudate putamen is situated in neuronal perikarya or at the terminals of striatal interneurons. The lack of effect of similar injections into the substantia nigra confirmed that the caudate putamen injections did not cause trans-synaptic changes. The presence of [³H]captopril binding is consistent with an ACE-mediated production of angiotensin II in some brain regions. Although [³H]captopril autoradiography reveals ACE in a striatonigral pathway, there is no evidence for angiotensin II involvement in such a neuronal pathway.