REGULATION OF THE ADENYLYL-CYCLASE SIGNALING SYSTEM IN VARIOUS TYPES OF CULTURED ENDOTHELIAL-CELLS

We studied the effects of modulators of the adenylyl cyclase pathway o n the accumulation of cAMP in endothelial cells isolated from bovine a ortas, pig pulmonary arteries, human umbilical veins, and human subcut aneous adipose microvessels. In addition to quantitative differences i n the basal levels, cAMP stimulation in different endothelial cell typ es varied in sensitivity and magnitude in response to both the direct adenylyl cyclase activator forskolin and the beta-adrenergic receptor agonist isoproterenol. Furthermore, the ubiquitous phosphodiesterase i nhibitor IBMX differentially enhanced both the basal and the stimulate d cAMP levels in the various cell types. Histamine caused an elevation of cAMP only in bovine aortic endothelial cells and in human umbilica l vein endothelial cells. Treatment of the cells with cholera and pert ussis toxins, which uniquely affect G-protein subunits, resulted in di vergent elevation of cAMP in the various cells. Thus, in each cell typ e, a distinct profile of regulation of the cAMP levels was found. Our results suggest that the adenylyl cyclase signaling system in various types of endothelial cells can be differentially regulated at the leve ls of receptors, G-proteins, adenylyl cyclase, and phosphodiesterase. (C) 1995 Wiley-Liss, Inc.