Regulation of phosphoinositide cycle by intracellular sodium in the blood-brain barrier.
In the present study of cerebral microvessels, we report that monensin, a Na+ ionophore, elicits a decrease in 32P radioactivity incorporation into phosphoinositides in cerebral microvessels. In addition, monensin evokes enhanced production of inositol-1-monophosphate (IP) and inositol-1,4-bisphosphate (IP2), together with an increase in the diacylglycerol (DAG) mass. These results indicate that monensin evokes a phosphoinositide hydrolysis by phospholipase C (PLC). The absence of inositol-1,4,5-trisphosphate (IP3) production leads us to think that although phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis occurs in this process, there is a very rapid disappearance of IP3. The net decrease in 32P radioactivity incorporated into phosphoinositides suggests that a partial inhibition of their re-synthesis is also evoked. Experimental evidence with pharmacological tools suggests that: (1) these effects are secondary to an increase in Ca2+ through the Na+/Ca2+ exchanger; and (2) the intracellular Ca2+ release is not involved in these effects of monensin. Since some neuropeptide receptors in cerebral microvessels have been reported to be coupled to either the Na+/H+ exchanger or to PLC, we discuss the possibility that cross-talk exists between these intracellular signalling pathways (phosphoinositide metabolism and Na+ transport) in the blood-brain barrier (BBB).
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
R E
RE
Catalán
A M
AM
Martínez
M D
MD
Aragonés
F
F
Hernández
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008985:Monensin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D010716:Phosphatidylinositols; D008985:Monensin; D012964:Sodium; D002118:Calcium