CROSS-TALK AMONG CYCLIC-AMP, CYCLIC-GMP, AND CA2-DEPENDENT INTRACELLULAR SIGNALING MECHANISMS IN BRAIN CAPILLARY ENDOTHELIAL-CELLS()

C-type natriuretic peptide and sodium nitroprusside, a nitric oxide do nor molecule, induced large increases in cyclic GMP formation in cultu red rat brain capillary endothelial cells. Isoproterenol, a potent ago nist of adenylate cyclase, potentiated the actions of C-type natriuret ic peptide and of sodium nitroprusside. These actions were not observe d in the presence of isobutylmethylxanthine and were mimicked by forsk olin. Endothelin-1 had no action on basal cyclic GMP levels. It reduce d cyclic GMP formation induced by C-type natriuretic peptide and sodiu m nitroprusside by about 50%. These actions involved an ET(A) receptor subtype and a Ca2+-dependent and protein kinase C-independent mechani sm. Finally, increasing cyclic GMP slightly prolonged intracellular Ca 2+ transients induced by endothelin-1. The results suggest the presenc e of extensive cross talk among cyclic AMP, cyclic GMP, and Ca2+-depen dent mechanisms in endothelial cells of brain microvessels. The releva nce of the results to the regulation of the blood-brain barrier permea bility is discussed.