Effects of Hypoxia on Muscarinic Cholinergic and Benzodiazepine/γ — Aminobutyric Acid Receptors in the Rat Brain

  • Haruaki Ninomiya
  • Takashi Taniguchi
  • Motohatsu Fujiwara
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 236)


Since electrophysiological studies showed that depletion of oxygen impairs the synaptic transmission as a primary focus (1 – 3), there are many reports related to the hypoxia-induced changes in neurotransmitter metabolism. It is now well established that in vivo exposure to mild hypoxia (20 % > 02 > 7 %) impairs the biosynthesis of various neurotansmitters in the brain including catecholamines (4 – 6), acetylcholine (ACh)(7 – 9) and amino acids (10 – 11), although such levels of hypoxia do not affect the cerebral energy metabolism (12 – 14). As for glucose-derived neurotransmitters, Gibson et al.(8) reported that incorporaton of 14C-glucose into ACh and γ-amino butyric acid (GABA) in the rat brain in vivo was significantly decreased by exposure to mild hypoxia (10 % 02, 90 % N2). These authors considered that the decrease in ACh synthesis is not due to the impairment of choline acetyltransferase (ChAT) activity but due to the impairment of the utilization of acetyl donors in ACh synthesis (15). Effect of exposure to hypoxia on the ChAT activity, however, was not examined. Bowen et al. (16), from postmortem studies of brains from patients suffering from cerebral hypoxia secondary to cardiovascular disease, showed that hypoxic brains exhibit decreased glutamic acid decarboxylase (GAD) activities when compared to the brains of control patients. These data indicate an impairment of GABA synthesis in presynaptic terminals under hypoxic conditions. However, controlled studies of the effects of hypoxia on GAD activity are lacking.


Glutamic Acid Decarboxylase Scatchard Analysis ChAT Activity Mild Hypoxia Saturation Isotherm 
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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Haruaki Ninomiya
    • 1
  • Takashi Taniguchi
    • 1
  • Motohatsu Fujiwara
    • 1
  1. 1.Department of Pharmacology, Faculty of MedicineKyoto UniversityKyotoJapan

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