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Intracellular Signals Coupled to Muscarinic Acetylcholine Receptor Activation in Cerebral Frontal Cortex from Hypoxic Mice

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Abstract

1. The aim of the present work was to determine hypoxia-induced modifications in the cascade of intracellular events coupled to muscarinic acetylcholine receptor (mAChR) activation in brain. For this purpose, enzymatic activities were measured on normoxically incubated frontal cortical slices from mice exposed to hypobaric hypoxia for 72 hr.

2. We found that hypoxia induced alterations in several cerebral enzymatic basal activities: it increased nitric oxide synthase (NOS), but it decreased both membrane protein kinase C (PKC) and phospholipase C activities.

3. The mAChR agonist carbachol was found to increase phosphoinositide hydrolysis to greater values in hypoxic tissues than those found in normoxic conditions. Furthermore, a greater translocation of PKC in response to carbachol was observed in hypoxic tissues than in normoxic ones.

4. Besides, carbachol induced a drastic reduction of NOS activity in hypoxic brains, at concentrations that stimulated this enzyme activity in normoxic preparations. In the latter, inhibition is obtained only with high concentrations of the cholinergic muscarinicagonist.

5. These results pointed to a carbachol-mediated mAChR hyperactivity induced by hypoxic insult.

6. The possibility that these effects would account for a compensatory mechanism to diminish NOS hyperactivity, probably protecting for NO neurotoxic action in hypoxic brain, is also discussed.

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Authors and Affiliations

  1. Centro de Estudios Farmacológicos y Botánicos, CEFYBO–CONICET, Buenos Aires, Argentina

    Tania G. Borda, Ana María Genaro & Graciela Cremaschi

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  1. Tania G. Borda
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  2. Ana María Genaro
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  3. Graciela Cremaschi
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Borda, T.G., Genaro, A.M. & Cremaschi, G. Intracellular Signals Coupled to Muscarinic Acetylcholine Receptor Activation in Cerebral Frontal Cortex from Hypoxic Mice. Cell Mol Neurobiol 20, 255–268 (2000). https://doi.org/10.1023/A:1007053907569

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