Lee, Dennis K
(Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada)
,
George, Susan R
(Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada)
,
O'Dowd, Brian F
(Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada)
,
George, Susan R
(Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada)
,
George, Susan R
(Centre for Addiction and Mental Health, Toronto, Ontario M5S 2S1, Canada)
,
O'Dowd, Brian F
(Centre for Addiction and Mental Health, Toronto, Ontario M5S 2S1, Canada)
,
Evans, Jilly F
(Department of Pharmacology, Merck and Co. Inc, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486, USA)
,
Lynch, Kevin R
(Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA)
AbstractThe majority of genes encoding G protein-coupled receptors were isolated by methods based on sequence similarities found throughout this family. Experimental techniques have exploited these similarities (including low-stringency hybridization, polymerase chain reaction and electronic databas...
AbstractThe majority of genes encoding G protein-coupled receptors were isolated by methods based on sequence similarities found throughout this family. Experimental techniques have exploited these similarities (including low-stringency hybridization, polymerase chain reaction and electronic database searching) to identify genes encoding many pharmacologically recognized receptors and their subtypes. Homology-based searches have revealed receptors for which the endogenous ligands were unknown and these were named orphan receptors. Many orphan receptors are expressed in the brain, suggesting the existence of unidentified neurotransmitters. Methods used to identify ligands for these orphan receptors resulted in the identification of novel ligands and succeeded in pairing previously identified ligands with their receptors. Similar successful strategies are required to characterize the physiological and pathological importance of the remaining orphan receptors to facilitate the discovery of novel drugs for these systems.
AbstractThe majority of genes encoding G protein-coupled receptors were isolated by methods based on sequence similarities found throughout this family. Experimental techniques have exploited these similarities (including low-stringency hybridization, polymerase chain reaction and electronic database searching) to identify genes encoding many pharmacologically recognized receptors and their subtypes. Homology-based searches have revealed receptors for which the endogenous ligands were unknown and these were named orphan receptors. Many orphan receptors are expressed in the brain, suggesting the existence of unidentified neurotransmitters. Methods used to identify ligands for these orphan receptors resulted in the identification of novel ligands and succeeded in pairing previously identified ligands with their receptors. Similar successful strategies are required to characterize the physiological and pathological importance of the remaining orphan receptors to facilitate the discovery of novel drugs for these systems.
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