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Further studies on the mechanism of action of substance P in rat brain, involving selective phosphatidylinositol hydrolysis

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Abstract

We have suggested that substance P, in cerebral cortex, causes a phosphatidylinositol (PI) breakdown by a dual mechanism suggesting the involvement of either phospholipase A2 or phospholipase C. We have presently characterized further these effects. Substance P (65 pM) provoked an increase in lysoPI concomitant with a decrease in PI level. This finding confirms the involvement of phospholipase A2 activation. To study the involvement of phospholipase C in the action of higher doses (0.65 μM) of the peptide, we used pulse-chase experiments (where phospholipid depletion was monitored) and short-term32P-labeled slices (where phospholipid synthesis was studied). Substance P evoked an acceleration of both hydrolysis and resynthesis of PI as early as 15 s. A prolonged exposure (30 min) resulted in stimulation of PI hydrolysis without subsequent resynthesis. The peptide did not cause any effect on inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate. These alterations in PI metabolism take place simultaneously with a generation of diacylglycerol which showed two maxima at both indicated times.

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Authors and Affiliations

  1. Departamento de Biología Molecular, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autónoma de Madrid, E-28049, Madrid, Spain

    R. E. Catalán, F. Hernández & A. Liras

  2. Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, E-28040, Madrid, Spain

    A. M. Martínez, M. D. Aragonés & B. G. Miguel

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  1. R. E. Catalán
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  2. A. M. Martínez
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  3. M. D. Aragonés
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  4. F. Hernández
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  5. A. Liras
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  6. B. G. Miguel
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Catalán, R.E., Martínez, A.M., Aragonés, M.D. et al. Further studies on the mechanism of action of substance P in rat brain, involving selective phosphatidylinositol hydrolysis. Neurochem Res 20, 1147–1153 (1995). https://doi.org/10.1007/BF00995377

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