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 transmembrane domains and interact with heteromeric G-proteins to transduce cellular signals. For a number of years our studies have focused on understanding the molecular mechanisms that modulate opiold receptors; these receptors are activated by binding to classic opiates such as morphine. Opioid receptor function is modulated by multiple mechanisms; this application is focused on exploring receptor dimerization-a novel mechanism that has been proposed to regulate opioid receptor function. Studies in specific aim # 1 will focus on characterizing the properties of heterodimers between opioid receptor types (i.e. mu and delta opioid receptors) using biochemical, biophysical and pharmacological techniques. Studies in specific aim # 2 will focus on studying novel interactions between opioid and other G-protein coupled receptors (i.e. alpha2 adrenergic, D2 dopamine and CB 1 cannabinoid receptors). Studies in specific aim # 3 will focus on the domains and residues involved in dimenzation in order to help define the interface of the receptor involved dimerization. These studies would facilitate future studies to develop dimerization deficient mutants; availability of such mutants would allow investigations to critically evaluate the role of dimenzation in receptor function. The studies described in this grant application will provide critical information on early events such as dimerization that regulate opioid receptor function. Elucidation of these novel cellular pathways involved in modulation of receptor function is a compelling strategy for identifying appropriate pharmacological interventions for drug addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA008863-12
Application #
6876694
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (01))
Program Officer
Koustova, Elena
Project Start
1995-03-15
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
12
Fiscal Year
2005
Total Cost
$339,000
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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