The primary object of this project is to examine the cellular and molecular properties of neuronal receptors for two neuropeptides, Angiotensin II (AngII) and oxytocin (OT). That each of these peptides play prominent and opposing roles in the central regulation of sodium appetite is now well established: AngII as a major stimulatory peptide and OT as a mediator of inhibition. The proposed experiments are divided into three main sections. In the first section, the Principal Investigator and his associates will continue their study of the regulation of these neuropeptide receptors in brain by adrenal steroid hormones. In the second series of experiments, they will examine further the cellular actions of AngII and OT and determine how these effects are modulated by adrenal steroids. These experiments will include the use of antisense oligonucleotides to interfere, specifically and reversibly, with the expression of protein (i.e., receptors, G-proteins, and enzymes) involved in AngII and OT action in brain to study directly their involvement in sodium appetite. In the final set of experiments, the researchers will explore some of the possible mechanisms for the sexual dimorphism of sodium appetite, ascertaining the relative contributions of excitatory and inhibitory neuropeptides during estrogen modulation of salt ingestion. Collectively, these experiments should provide a fuller understanding of the cellular mechanisms that mediate neuropeptide control of salt appetite, as well as fundamental insights into the neuroendocrinology of behavior.
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