SIGNIFICANCE OF THE SECOND MESSENGER MOLECULES IN THE REGULATION OF CEREBRAL ENDOTHELIAL CELL FUNCTIONS

Several receptors for different vasoactive substances have been shown to be coupled to the microvascular adenylate cyclase and to increase the intraendothelial amount of cyclic AMP (Joo, 1986, 1992, 1993). As a consequence of elevated intraendothelial cyclic AMP, changes in permeability (Joo, 1972; Rubin et al. 1991), in endothelial growth and differentiation (Kempski et al. 1987), in nitric oxide and endothelin secretions (Durieu-Trautmann et al. 1993) and in a hyperpolarization-activated current carried by both Na+ and K+ ions (Janigro et al. 1994) have been reported. Elevations of cyclic AMP concentrations may be important in regulating the endothelial barrier in two-ways: (i) by narrowing the paracellular pathways for small molecular weight substances (Rubin et al. 1991), and (ii) activating the transendothelial transport for macromolecules (Joo, 1972). Recently, Grammas et al. (1994) found significantly elevated cAMP levels in microvessels from Alzheimer’s disease compared to nondemented elderly controls.