Intracellular sigma1 receptor modulates phospholipase C and protein kinase C activities in the brainstem.
Most physiological effects of sigma1 receptor ligands are sensitive to pertussis toxin, suggesting a coupling with cell membrane-bound G proteins. However, the cloning of the sigma1 receptor has allowed the identification of an intracellular protein anchored on the endoplasmic reticulum. Here, we show, using the isolated adult guinea pig brainstem preparation, that activation of the sigma1 receptor results in its translocation from the cytosol to the vicinity of the cell membrane and induces a robust and rapid decrease in hypoglossal activity, which is mediated by phospholipase C. The subsequent activation of protein kinase C beta1 and beta2 isoforms and the phosphorylation of a protein of the same molecular weight as the cloned sigma1 receptor lead to a desensitization of the sigma1 motor response. Our results indicate that the intracellular sigma1 receptor regulates several components implicated in plasma membrane-bound signal transduction. This might be an example of a mechanism by which an intracellular receptor modulates metabotropic responses.
Morin-Surun
M P
MP
Institut Alfred Fessard, avenue de la Terrasse, 91198 Gif-sur Yvette, France. morin@iaf.cnrs.gif.fr
Collin
T
T
Denavit-Saubié
M
M
Baulieu
E E
EE
Monnet
F P
FP
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008024:Ligands; D008297:Male; D010423:Pentazocine / Q000494:pharmacology; D037342:Pertussis Toxin; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D017480:Receptors, sigma / Q000235:genetics / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D014150:Antipsychotic Agents; D007527:Isoenzymes; D008024:Ligands; D017480:Receptors, sigma; D010566:Virulence Factors, Bordetella; C101491:sigma1-binding protein, rat; C012134:SK&F 10047; D037342:Pertussis Toxin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D010620:Phenazocine; D006220:Haloperidol; D010423:Pentazocine