ROLE OF NEUROPEPTIDES AND BIOGENIC AMINES IN BRAIN FUNCTION

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We continued our studies on angiotensin II and other neuropeptide and biogenic amine receptors. We cloned a new angiotensin II receptor, highly localized to the hippocampus of the gerbil, with possible function in neuronal plasticity. Molecular studies revealed the domain likely to determine affinity for receptor inhibitors. Using receptor deficient mice, we found that the expression of brain angiotensin receptor subtypes was dependent not only on the brain area, but, in some areas, on the species studied. We identified, in the dorsal arcuate nucleus, a sexually dimorphic area for angiotensin AT1 receptors. These receptors are up-regulated by estrogen and progesterone in the female, are involved in the secretion of prolactin, and they are made by dopaminergic neurons. Thus, we showed for the first time a cellular linkage between the angiotensin and catecholamine systems in the brain. We completed the localization of receptor expression and mRNA for AT1 and AT2 angiotensin receptor subtypes in the olivo-cerebellar pathway, and obtained data indicative of a transport of AT2 receptors via climbing fibers from the inferior olive to the cerebellar cortex.