Differential membrane targeting and pharmacological characterization of chimeras of rat serotonin 5-HT1A and 5-HT1B receptors expressed in epithelial LLC-PK1 cells

J Neurochem. 1998 Dec;71(6):2294-303. doi: 10.1046/j.1471-4159.1998.71062294.x.

Abstract

The serotonin 5-HT1A and 5-HT1B receptors are two structurally related but pharmacologically distinguishable 5-HT receptor types. In brain, the 5-HT1A receptor is localized on the soma and dendrites of neurons, whereas the 5-HT1B receptor is targeted to the axon terminals. We previously showed that these two receptors are targeted in different membrane compartments when stably expressed in the epithelial LLC-PK1 cell line. Further investigations on the mechanisms responsible for their differential targeting were done by constructing chimeras of 5-HT1A and 5-HT1B receptors still able to bind specifically [3H]lysergic acid diethylamide and selective agonists and antagonists. Their cellular localization examined by confocal microscopy suggests that the third intracellular domain of the 5-HT1B receptor was responsible for its Golgi-like localization in transfected LLC-PK1 cells. In contrast, the third intracellular domain of the 5-HT1A receptor apparently allowed the sorting of the chimeras to the plasma membrane. Further inclusion of the C-terminal domain of the 5-HT1A receptor in their sequence led to a basolateral localization, whereas that of the 5-HT1B receptor allowed an apical targeting, suggesting the existence of a targeting signal in this portion of the receptor(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chimera / genetics*
  • Epithelial Cells / metabolism
  • Intracellular Membranes / metabolism
  • Isomerism
  • LLC-PK1 Cells
  • Molecular Sequence Data
  • Rats
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / metabolism
  • Serotonin Receptor Agonists / metabolism
  • Swine
  • Tissue Distribution

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists