Central mu- and kappa-opioid agonists evoke profound changes in urine flow rate and urinary sodium excretion via multiple integrated neural and physiological mechanisms. In addition to these subtypes, a novel opioid-like peptide, nociceptin, and opioid receptor, the ORL1 receptor, have recently been identified. Despite their structural resemblance to endogenous opioid peptides and receptors, the role of nociceptin and the ORL1 receptor in the regulation of renal function, is not known. My short-term goals are to characterize the renal responses produced by activation of the central nociceptin system on renal hemodynamic and excretory function in conscious Sprague-Dawley rats. In addition, the neural and humoral mechanisms, as well as brain sites (e.g. paraventricular nucleus) by which this novel central opioid-like system affects renal function will be investigated. My long-term objectives are to understand the physiological role of the endogenous central nociceptin system in the regulation of renal function and determine how this system interacts with classical opioid systems in this regulatory process. Since to date an antagonist for the ORL1 receptor has not been developed, the role of the endogenous central nociceptin system in the regulation of renal function during basal and stressful environmental conditions will be examined by use of in vivo molecular biology techniques (antisense oligodeoxynucleotide). The funding of an RCDA will help me to accomplish the goals outlined above and to further develop and strengthen my scientific career. In this regard, an RCDA will relieve me from Departmental obligations such as teaching in medical, dental, nursing and allied health courses, and from my substantial duties as Graduate Coordinator for the Department of Pharmacology. I will also be exempt from service on additional committees, both at the Departmental and University level. Together, by securing this award I will be able to devote essentially a full-time effort to my cardiovascular and renal research. The Department of Pharmacology and LSU Medical center provide a supportive environment for the development of my research career. Service is available from the LSUMC Biotechnology Unit for the synthesis of the antisense oligodeoxynucleotides. Facilities are also available within the University for computer and statistical consultation. There also exists a number of other basic research and clinical scientists that maintain active research programs in cardiovascular and renal physiology. The fact that Department faculty receive considerable support from federal granting agencies means that expertise and equipment is readily available. In summary, an RCDA will greatly enhance my research productivity and scientific career.
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