Abstract
The actions of many hormones and neurotransmitters are mediated by the members of a superfamily of receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins). These receptors are characterized by a highly conserved topographical arrangement in which seven transmembrane domains are connected by intracellular and extracellular loops. The interaction between these receptors and G proteins is mediated in large part by the third intracellular loop of the receptor. Coexpression of the third intracellular loop of the alpha 1B-adrenergic receptor with its parent receptor inhibited receptor-mediated activation of phospholipase C. The inhibition extended to the closely related alpha 1C-adrenergic receptor subtype, but not the phospholipase C-coupled M1 muscarinic acetylcholine receptor nor the adenylate cyclase-coupled D1A dopamine receptor. These results suggest that the receptor-G protein interface may represent a target for receptor antagonist drugs.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Cell Line
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Cloning, Molecular
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Cyclic AMP / metabolism
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Cytoplasm / metabolism
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GTP-Binding Proteins / metabolism*
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Globins / genetics
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Humans
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Inositol Phosphates / metabolism
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Kinetics
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Molecular Sequence Data
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Muscarinic Antagonists
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Oligodeoxyribonucleotides
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Plasmids
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Protein Structure, Secondary
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Receptors, Adrenergic, alpha / genetics
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Receptors, Adrenergic, alpha / metabolism*
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Receptors, Dopamine D1 / antagonists & inhibitors
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Receptors, Dopamine D1 / genetics
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Receptors, Dopamine D1 / metabolism*
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Receptors, Muscarinic / genetics
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Receptors, Muscarinic / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction*
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Transfection
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Type C Phospholipases / metabolism
Substances
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Inositol Phosphates
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Muscarinic Antagonists
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Oligodeoxyribonucleotides
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Receptors, Adrenergic, alpha
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Receptors, Dopamine D1
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Receptors, Muscarinic
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Recombinant Fusion Proteins
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Globins
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Cyclic AMP
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Glutathione Transferase
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Type C Phospholipases
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GTP-Binding Proteins