ROLE OF NEUROPEPTIDES AND BIOGENIC AMINES IN NEUROENDOCRINE REGULATION

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1. Brain angiotensin receptor subtypes. We have continued our studies to characterize brain angiotensin receptor subtypes and to establish their function. Comparison between species (rat, mice and gerbil) gave us new clues as to the regulation and function of these subtypes. We have obtained a cDNA clone of the novel 'atypical' gerbil receptor. We determined that selective receptor subtypes are involved in the central regulation of fluid metabolism and in the central effects of reproductive hormones. Using models of receptor deficient mice, we clarified that brain AT2 receptors are encoded by a single gene. AT2 receptors have been further localized to specific neurons within the inferior olivary-cerebellar system. Substantial differences in the expression of receptor subtypes in the brain were found after comparison of rat, mice and gerbil brains. 2. Peripheral angiotensin receptor subtypes. Large differences in angiotensin receptor subtype expression were also found during the process of skin wound repair. 3. Novel macrophage/microglial receptor. Binding of CGP 42112 to the novel non-angiotensin macrophage receptor inhibits human macrophage activation and probably mediates anti inflammatory responses. This binding is high in inflammatory tissue surrounding arteries after arterial lesions, and may play a role in arteriosclerosis and arterial injury. We continue our efforts to clone the novel macrophage/microglia receptor from a cDNA library from human monocytes.