OHSU

Olsen Lab

The long-term goal of my research is to understand the mechanism by which chronic in utero morphine and methadone exposures alter function of mu opioid receptors (MOP) in specific respiratory control areas of neonatal brainstem. A critical brainstem site for opioid respiratory effects is the nucleus tractus solitarius (NTS) in the medulla, an area responsible for integration of information from the pons, other medullary sites, and the periphery, and for driving muscles of inspiration. Drug dependence alters normal respiratory control by affecting MOP and subsequent cell signaling. MOP is a cell surface G-protein linked receptor.  Mu opioid agonists bind to MOP, stimulate guanosine triphosphate (GTP) binding to G-proteins, and initiate cell signals that increase potassium and decrease calcium conductance in nerves. These cellular actions lead to depressed neural function and respiration. There is evidence that chronic opioid exposure up-regulates MOP, but decreases efficiency of coupling between MOP activation and function of G-proteins. We have determined the guinea pig MOP cDNA sequence and expressed the MOP in Chinese hamster ovary cells in order to characterize the receptor for ligand binding and G-protein activation. In addition we compared the receptor with the human and rat receptor and applied this information to the problem of drug dependence.

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