The primary objective of this project is to investigate the cellular and molecular properties of neuronal receptors for two neuropeptides, angiotensin II (AngII) and oxytocin (OT). It is now well established that each of these peptides play prominent and opposing roles in the central regulation of sodium appetite; 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, we will continue our investigations of the regulation of these neuropeptide receptors in brain by adrenal steroid hormones. In the second series of experiments, we will further investigate 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 specifically and reversibly interfere with the expression of proteins (i. e. receptors, G- proteins and enzymes) involved in AngII and OT action in brain to directly examine their involvement in sodium appetite. In the final set of experiments, we 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.
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