Enhancement of histamine H1-receptor agonist activity by 1,4-dithiothreitol in guinea-pig cerebellum and cerebral cortex

J Neurochem. 1986 Nov;47(5):1476-82. doi: 10.1111/j.1471-4159.1986.tb00781.x.


The disulphide bond-reducing agent 1,4-dithiothreitol (1 mM) produced a marked potentiation of histamine-stimulated accumulation of [3H]inositol phosphates in lithium-treated slices of guinea-pig cerebellum and cerebral cortex. This was seen as a parallel shift of the concentration-response curve for histamine to lower agonist concentrations, with no significant effect on the maximal response or Hill coefficient. Dithiothreitol similarly potentiated the augmentation of adenosine-stimulated cyclic AMP accumulation elicited by histamine in guinea-pig cerebral cortex. Studies with partial agonists suggested that this potentiating effect was associated with an increase in agonist efficacy rather than a change in agonist binding affinity. Thus, dithiothreitol increased the maximal accumulation of [3H]inositol phosphates produced by both 2-pyridylethylamine and 2-methylhistamine, which appeared to act as partial agonists in guinea-pig cerebral cortex. Dithiothreitol similarly increased the maximal extent of the augmentation of adenosine-stimulated accumulation of cyclic AMP produced by 2-methylhistamine. The site of action of dithiothreitol is not known; however, a comparison of the effect of dithiothreitol on muscarinic and histamine H1-receptor-mediated phosphoinositide responses in guinea-pig cerebral cortex suggests that it is before the stage at which the receptor-effector pathways are shared by these two receptor systems.

MeSH terms

  • Animals
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cyclic AMP / metabolism
  • Dithiothreitol / pharmacology*
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Mathematics
  • Methylhistamines / pharmacology
  • Phosphatidylinositols / metabolism
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H1 / metabolism*


  • Methylhistamines
  • Phosphatidylinositols
  • Receptors, Histamine
  • Receptors, Histamine H1
  • Cyclic AMP
  • 2-methylhistamine
  • Dithiothreitol