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 (32)LP 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 P-32 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 he coupled to either the Na+/H+ exchanger or re, 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).