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 incorpor ation into phosphoinositides in cerebral microvessels. In addition, mo nensin evokes enhanced production of inositol-1-monophosphate: (IP) an d inositol-1,4-bisphosphate (IP2), together with an increase in the di acylglycerol (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 a lthough 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 sug gests that a partial inhibition of their re-synthesis is also evoked. Experimental evidence with pharmacological tools suggests that: (1) th ese effects are secondary to an increase in Ca2+ through the Na+/Ca2exchanger; and (2) the intracellular Ca2+ release is not involved in t hese effects of monensin. Since some neuropeptide receptors in cerebra l microvessels have been reported to he coupled to either the Na+/H+ e xchanger or re, PLC, we discuss the possibility that cross-talk exists between these intracellular signalling pathways (phosphoinositide met abolism and Na+ transport) in the blood-brain barrier (BBB).