CA2-INHIBITABLE ADENYLYL-CYCLASE MODULATES PULMONARY-ARTERY ENDOTHELIAL-CELL CAMP CONTENT AND BARRIER FUNCTION()

Maintenance by the endothelium of a semipermeable barrier is criticall y important in the exchange of oxygen and carbon dioxide in the lung. Intracellular free Ca2+ ([Ca2+](i)) and cAMP are principal determinant s of endothelial cell barrier function through their mutually opposing actions on endothelial retraction. However, details of the mechanisms of this antagonism are lacking, The recent discovery that certain ade nylyl cyclases (EC 4.6.1.1) could be acutely inhibited by Ca2+ in the intracellular concentration range provided one possible mechanism wher eby elevated [Ca2+](i) could decrease cAMP content. This possibility w as explored in pulmonary artery endothelial cells. The results indicat e that a type Vi Ca2+-inhibitable adenylyl cyclase exists in pulmonary artery endothelial cells and is modulated by physiological changes in [Ca2+](i). Furthermore, the results suggest the inverse relationship between [Ca2+](i) and cAMP that is established by Ca2+-inhibitable ade nylyl cyclase plays a critical role in modulating pulmonary artery end othelial cell permeability. These data provide evidence that susceptib ility to inhibition of adenylyl cyclase by Ca2+ can be exploited in mo dulating a central physiological process.