Rediocide A, an Insecticide, induces G-protein-coupled receptor desensitization via activation of conventional protein kinase C

J Nat Prod. 2012 Jun 22;75(6):1058-62. doi: 10.1021/np3000359. Epub 2012 May 31.

Abstract

In order to identify small-molecule antagonists of Methuselah (Mth), a Drosophila G-protein-coupled receptor (GPCR) involved in life-span control, a library of natural compounds was screened, and it was found that rediocide A (1), a daphnane ester from the roots of Trigonostemon reidioides and used currently for flea control, potently inhibited calcium mobilization mediated by this receptor. Compound 1 inhibited calcium mobilization in GPCRs other than Mth, indicating that the inhibitory effect was not due to receptor antagonism but rather to a more general mechanism. It was found that 1 can induce GPCR desensitization and internalization, and such effects were mediated by the activation of conventional protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology*
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / drug effects
  • Insecticides / chemistry
  • Insecticides / pharmacology*
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Molecular Structure
  • Protein Kinase C / drug effects
  • Protein Kinase C / metabolism*
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Diterpenes
  • Drosophila Proteins
  • Insecticides
  • Macrolides
  • Receptors, G-Protein-Coupled
  • mth protein, Drosophila
  • rediocide A
  • mezerein
  • Protein Kinase C