Receptor-mediated activation of G proteins is reduced in postmortem brains from Alzheimer's disease patients

Neurosci Lett. 1994 May 23;173(1-2):37-9. doi: 10.1016/0304-3940(94)90144-9.

Abstract

The effects of Alzheimer's disease (AD) on [35S]GTP gamma S binding to G proteins was examined in postmortem cerebrocortex. Stimulation of the beta-adrenergic or muscarinic cholinergic receptors in control tissue with selective agonists resulted in increases in [35S]GTP gamma S binding to G alpha proteins in a receptor-specific fashion. The responses were markedly reduced in brain tissues from AD patients. In contrast, basal [35S]GTP gamma S binding to the G alpha proteins was relatively intact in AD brains. Immunoblot analyses reveal that levels of cerebrocortical G alpha proteins in AD are not altered. The results suggest that in AD the decrease in agonist-stimulated [35S]GTP gamma S binding to G proteins may be a result of decoupling between receptors and their associated G proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / metabolism*
  • Biotransformation / drug effects
  • Biotransformation / physiology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Carbachol / pharmacology
  • Female
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacokinetics
  • Humans
  • Immunoblotting
  • Isoproterenol / pharmacology
  • Male
  • Protein Binding
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Sulfur Radioisotopes

Substances

  • Receptors, Neurotransmitter
  • Sulfur Radioisotopes
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Carbachol
  • GTP-Binding Proteins
  • Isoproterenol