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Abstract

Grant Number:	1R03NS053751-01
Project Title:	Assay to Screen Ligands:Activate Opioid Receptor (RMI)

PI Information:	Name	Email	Title
	DEVI, LAKSHMI A.	lakshmi.devi@mssm.edu

Abstract: DESCRIPTION (provided by applicant): G-protein coupled receptors constitute the single largest family of cell surface receptors that mediate physiological responses to a wide variety of stimuli. These receptors are characterized by seven (7) transmembrane domains and interact with heterotrimeric G-proteins to transducer cellular signals. For a number of years our studies have focused on understanding the molecular mechanisms that modulate opioid receptors; these receptors are activated by binding to classic opiates such as morphine. Opioid receptor function is modulated by multiple mechanisms; we have focused on receptor dimerization as a novel mechanism to regulate opioid receptor function. We have characterized the properties of heterodimers between opioid receptor types (i.e. mu and delta opioid receptors) using biochemical, biophysical and pharmacological techniques. We have found that the mu receptor-mediated signaling in cells and analgesia in mice can be enhanced by a delta receptor antagonist. These results suggest that heterodimerization between mu and delta receptors leads modulation of the extent of signaling. In order to address the physiological consequences of mu delta heterodimerization, ligands that selectively activate or inactivate mu-delta heterodimers (without affecting the activities of mu or delta receptors) are needed. In this application we propose to develop a high throughput screening (HTS) assay to screen for ligands that selectively bind and activate mu-delta heterodimers. These studies will enable HTS screening and identification of small molecules that would be critical tools to probe the role of mu-delta heterodimers in vivo.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
dimer, drug discovery /isolation, drug screening /evaluation, high throughput technology, ligand, opioid receptor, receptor expression, technology /technique development
conformation, monoclonal antibody, small molecule
biotechnology

Institution:	MOUNT SINAI SCHOOL OF MEDICINE OF NYU
	OF NEW YORK UNIVERSITY
	NEW YORK, NY 100296574
Fiscal Year:	2005
Department:	PHARMACOLOGY & SYSTEMS THERAPEUTICS
Project Start:	30-SEP-2005
Project End:	30-NOV-2008
ICD:	NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG:	ZNS1

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