Molecular analysis of the regulation of muscarinic receptor expression and function

Susan E. Hamilton, Lise A. McKinnon, Darrell A. Jackson, Phyllis S. Goldman, Jacques C. Migeon, Beth A. Habecker, Sarabeth L. Thomas, Neil M. Nathanson

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Several systems are being used to determine the molecular and cellular basis for the regulation of expression and function of the muscarinic receptors. Treatment of chick heart cells in culture results in decreased levels of mRNA encoding the cm2 and cm4 receptors. This probably results from decreased gene transcription which requires concomitant mAChR-mediated inhibition of adenylyl cyclase and mAChR-mediated stimulation of phospholipase C. Site-directed mutagenesis was used to demonstrate that the single tyrosine residue in the carboxyl-terminal cytoplasmic tail of the m2 receptor is involved in agonist-induced downregulation but not sequestration. Activation of heterologous receptors in chick heart cells can also regulate mAChR mRNA levels. A cAMP-regulated luciferase reporter gene has been used to demonstrate that the m4 receptor preferentially couples to Giα-2 or Gα over Giθ-l or Gia-3 to mediate inhibition of adenylyl cyclase activity. Finally, in order to determine the role of individual receptor subtypes in muscarinic-mediated responses in vivo, we are beginning to use the method of targeted gene disruption by homologous recombination to generate mice deficient in specific receptor subtypes.

Original languageEnglish (US)
Pages (from-to)939-943
Number of pages5
JournalLife Sciences
Volume56
Issue number11-12
DOIs
StatePublished - Feb 10 1995

Keywords

  • G-protein
  • gene disruption
  • mRNA
  • muscarinic receptor
  • transfection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Hamilton, S. E., McKinnon, L. A., Jackson, D. A., Goldman, P. S., Migeon, J. C., Habecker, B. A., Thomas, S. L., & Nathanson, N. M. (1995). Molecular analysis of the regulation of muscarinic receptor expression and function. Life Sciences, 56(11-12), 939-943. https://doi.org/10.1016/0024-3205(95)00031-Z