Antagonism of catecholamine receptor signaling by expression of cytoplasmic domains of the receptors

Science. 1993 Mar 5;259(5100):1453-7. doi: 10.1126/science.8383880.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Cytoplasm / metabolism
  • GTP-Binding Proteins / metabolism*
  • Globins / genetics
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Humans
  • Inositol Phosphates / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Muscarinic Antagonists
  • Oligodeoxyribonucleotides
  • Plasmids
  • Protein Structure, Secondary
  • Receptors, Adrenergic, alpha / genetics
  • Receptors, Adrenergic, alpha / metabolism*
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Muscarinic / genetics
  • Receptors, Muscarinic / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Transfection
  • Type C Phospholipases / metabolism

Substances

  • Inositol Phosphates
  • Muscarinic Antagonists
  • Oligodeoxyribonucleotides
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine D1
  • Receptors, Muscarinic
  • Recombinant Fusion Proteins
  • Globins
  • Cyclic AMP
  • Glutathione Transferase
  • Type C Phospholipases
  • GTP-Binding Proteins