Angiotensin converting enzyme in the human basal forebrain and midbrain visualized by in vitro autoradiography

angiotensin converting enzyme converts angiotensin I to angiotensin II, a peptide that plays an important role in the central regulation of blood pressure and fluid and electrolyte homeostasis. However, the distribution of this enzyme in the human brain has not been well described. In this study, angiotensin converting enzyme was mapped in the human basal forebrain and midbrain by using quantitative in vitro autoradiography employing a derivative of a potent converting enzyme inhibitor, 125I-351A, as radioligand. This radioligand binds specifically and with high affinity to angiotensin converting enzyme and also exhibited these properties in binding to slide-mounted sections of human basal ganglia. In the basal ganglia, high levels of binding of 125I-351A are found in the caudate nucleus, putamen, nucleus accumbens, both divisions of the globus pallidus, and substantia nigra pars reticulata. High densities of labelling also occur in the ventral pallidum. In the hypothalamus, a moderate level occurs in the paraventricular and supraoptic nuclei, and a diffuse, low level of binding is found throughout the periventricular region. The organum vasculosum of the lamina terminalis, one of the circumventricular organs, displays the highest concentration of binding. The choroid plexus contains only moderate density of labelling in contrast to other mammalian species previously studied. Major fibre tracts are devoid of activity except for the posterior limb of the internal capsule, which contains fascicles of intense activity. In the midbrain, a moderate density of binding is detected in the periaqueductal gray. The dorsal, central linear, and, more caudally, the centralis superior medialis raphe nuclei also contain moderate densities of labelling. Angiotensin converting enzyme is heterogeneously distributed in the caudate nucleus and putamen, with distinct patches of high concentration surrounded by a matrix of diffuse, lower levels. In the caudate nucleus, these patches of high binding corresponded to striosomes since they register with acetylcholinesterase-poor zones. The high concentration of angiotensin converting enzyme found in the basal ganglia suggests that the enzyme may be involved in processing neuropeptides that occur in high concentrations in these structures. Possible substrates for converting enzyme include not only angiotensin I but also substance P and enkephalins, which are also concentrated in striosomes.