Further studies on the mechanism of action of substance P in rat brain, involving selective phosphatidylinositol hydrolysis.
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 microM) of the peptide, we used pulse-chase experiments (where phospholipid depletion was monitored) and short-term 32P-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.
Catalán
R E
RE
Departamento de Biología Molecular, Universidad Autónoma de Madrid, Spain.
Martínez
A M
AM
Aragonés
M D
MD
Hernández
F
F
Liras
A
A
Miguel
B G
BG
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*
D010716:Phosphatidylinositols; D013373:Substance P