DISTRIBUTION OF AT(4) RECEPTORS IN THE MACACA-FASCICULARIS BRAIN

Angiotensin IV (Val Tyr Ile His Pro Phe), administered centrally, incr eases memory retrieval and induces c-fos expression in the hippocampus and piriform cortex. Angiotensin IV binds to a high affinity site tha t is quite distinct in pharmacology and distribution from the angioten sin II AT(1) and AT(2) receptors and is known as the AT(4) receptor. T hese observations suggest that the AT(4) receptor may have multiple ce ntral effects. The present study uses in vitro receptor autoradiograph y, and employs [I-125]angiotensin IV to map AT(4) receptors in the mac aca fascicularis brain. The distribution of the AT(4) receptor is rema rkable in that its distribution extends throughout several neural syst ems. Most striking is its localization in motor nuclei and motor assoc iated regions. These include the ventral horn spinal motor neurons, al l cranial motor nuclei including the oculomotor, abducens, facial and hypoglossal nuclei, and the dorsal motor nucleus of the vagus. Recepto rs are also present in the vestibular, reticular and inferior olivary nuclei, the granular layer of the cerebellum, and the Betz cells of th e motor cortex. Moderate AT(4) receptor density is seen in all cerebel lar nuclei, ventral thalamic nuclei and the substantia nigra pars comp acta, with lower receptor density observed in the caudate nucleus and putamen. Abundant AT(4) receptors are also found in areas associated w ith cholinergic nuclei and their projections, including the nucleus ba salis of Meynert, ventral limb of the diagonal band and the hippocampu s, somatic motor nuclei and autonomic preganglionic motor nuclei. AT(4 ) receptors are also observed in sensory regions, with moderate levels in spinal trigeminal, gracile, cuneate and thalamic ventral posterior nuclei, and the somatosensory cortex. The abundance of the AT(4) rece ptor in motor and cholinergic neurons, and to a lesser extent, in sens ory neurons, suggests multiple roles for the AT(4) receptor in the pri mate brain.