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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK052018-01
Application #
2017564
Study Section
Special Emphasis Panel (ZRG2-BPO (01))
Program Officer
Smith, Philip F
Project Start
1997-02-15
Project End
2001-12-31
Budget Start
1997-02-15
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Griffin, Gerald D; Flanagan-Cato, Loretta M (2009) Sex differences in the dendritic arbor of hypothalamic ventromedial nucleus neurons. Physiol Behav 97:151-6
Daniels, Derek; Mietlicki, Elizabeth G; Nowak, Erica L et al. (2009) Angiotensin II stimulates water and NaCl intake through separate cell signalling pathways in rats. Exp Physiol 94:130-7
Labelle, Denise R; Cox, Julia M; Dunn-Meynell, Ambrose A et al. (2009) Genetic and dietary effects on dendrites in the rat hypothalamic ventromedial nucleus. Physiol Behav 98:511-6
Patten, Caroline S; Daniels, Derek; Suzuki, Aae et al. (2007) Structural and signaling requirements of the human melanocortin 4 receptor for MAP kinase activation. Regul Pept 142:111-22
Daniels, Derek; Yee, Daniel K; Fluharty, Steven J (2007) Angiotensin II receptor signalling. Exp Physiol 92:523-7
Flanagan-Cato, L M; Calizo, L H; Griffin, G D et al. (2006) Sexual behaviour induces the expression of activity-regulated cytoskeletal protein and modifies neuronal morphology in the female rat ventromedial hypothalamus. J Neuroendocrinol 18:857-64
Yee, Daniel K; Suzuki, Aae; Luo, Laiyi et al. (2006) Identification of structural determinants for G protein-independent activation of mitogen-activated protein kinases in the seventh transmembrane domain of the angiotensin II type 1 receptor. Mol Endocrinol 20:1924-34
Daniels, Derek; Yee, Daniel K; Faulconbridge, Lucy F et al. (2005) Divergent behavioral roles of angiotensin receptor intracellular signaling cascades. Endocrinology 146:5552-60
Daniels, Derek; Fluharty, Steven J (2004) Salt appetite: a neurohormonal viewpoint. Physiol Behav 81:319-37
Daniels, Derek; Patten, Caroline S; Roth, Jonathan D et al. (2003) Melanocortin receptor signaling through mitogen-activated protein kinase in vitro and in rat hypothalamus. Brain Res 986:1-11

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