Involvement of calcium in phosphoinositide metabolism in the blood-brain barrier.
The Ca2+ effect on phosphoinositide metabolism in the blood-brain barrier was studied by using rat cerebral microvessels prelabelled with either [32P]orthophosphate or myo-[3H]inositol and stimulated with Ca2+ ionophore A23187. In radioactivity steady-state conditions, addition of ionophore caused a rapid and marked loss of labelling in both phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2), without significant alterations in phosphatidylinositol (PI) and phosphatidic acid (PA) labelling. These facts were accompanied by a rise in labelling of both inositol 1-monophosphate (IP) and inositol 1,4-bisphosphate (IP2), but not in inositol 1,4,5-trisphosphate (IP3). In addition, a Ca(2+)-dependent inhibition of phosphoinositide kinase activities from isolated membranes was also found. These data suggest that elevated intracellular Ca2+ level evokes a PIP and PIP2 hydrolysis by phosphodiesterasic and phosphomonoesterasic activities respectively, and also partially inhibits the synthesis of these phosphoinositides. Our results constitute evidence that a reciprocal control mechanism between polyphosphoinositide metabolism and mobilization of Ca2+ exists in the blood-brain barrier.
Catalán
R E
RE
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
Martínez
A M
AM
Aragonés
M D
MD
Fernández
I
I
Hernández
F
F
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D002560:Cerebrovascular Circulation; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D000001:Calcimycin; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D002118:Calcium