Characterization of 5-HT2A receptor desensitization and the effect of cycloheximide on it in C6 cells

J Neural Transm (Vienna). 2001;108(3):249-60. doi: 10.1007/s007020170070.

Abstract

Effect of prolonged pretreatment with serotonin (5-HT) on 5-HT2A receptor desensitization was examined by the measurement of intracellular calcium ([Ca2+]i) mobilization in C6 cells. 5-HT-induced desensitization of [Ca2+]i mobilization was in a time and dose dependent manner and reached a plateau after 3 hr. After 1 and 3 hr 5-HT pretreatment, 5-HT concentration in the medium little changed. 5-HT pretreatment with cycloheximide, a protein synthesis inhibitor, produced an enhancement of the desensitization for 3 and 6 hr pretreatment. However, 5-HT pretreatment for 3 and 6 hr caused no marked change in the 5-HT2A receptor mRNA level or Galphaq/11 protein in this study, suggesting that 5-HT may decrease 5-HT-induced [Ca2+]i mobilization independent of 5-HT2A receptor mRNA or G-proteins. Endothelin-1-induced [Ca2+]i mobilization did not alter after 5-HT and/or cycloheximide pretreatment. These results showed that activation of the 5-HT2A receptor induced homologous desensitization and pretreatment with 5-HT and/or cycloheximide did not change the efficacy of the second messenger pathway from Gq to a [Ca2+]i rise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cycloheximide / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology*
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Glioma
  • Heterotrimeric GTP-Binding Proteins / drug effects
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism
  • Protein Synthesis Inhibitors / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Rats
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Endothelin / drug effects
  • Receptors, Endothelin / metabolism
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism
  • Serotonin / pharmacology*
  • Tumor Cells, Cultured / drug effects*
  • Tumor Cells, Cultured / metabolism

Substances

  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Endothelin
  • Receptors, Serotonin
  • Serotonin
  • Cycloheximide
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins
  • Calcium