Regional differentiation in the rat aorta for a novel signaling pathway: leucine to glutamate

Rat aortic endothelium is differentiated regionally for regulating guanosine 3',5'-cyclic monophosphate (cGMP) levels in underlying smooth muscle by signaling via nitric oxide and prostaglandin H2. Highest activity is just distal to the aortic arch and diminishes peripherally. The same differentiation pattern is reported here for a third and novel signal pathway: endothelial conversion of L-leucine to L-glutamate. Sequential segments of rat aorta incubated in vitro convert L-[U-14C]leucine to a major 14C metabolite identified as L-glutamate. Net synthesis of glutamate is greatest in aortic segments of the "windkessel" region; significant quantities are also observed in the pancreas, testis, and lung but very little in 10 additional tissues. Endothelial cells cultured from mouse brain, human umbilical vein, or bovine aorta and human peripheral blood macrophages also form [14C]glutamate. When aortic segments are denuded of endothelium, treatment with L-glutamate in the presence of 3-isobutyl-1-methylxanthine significantly increases the cGMP content. A number of leucine derivatives inhibit the leucine-to-glutamate conversion and decrease the cGMP content in aortic segments in vitro.