REGIONAL DIFFERENTIATION IN THE RAT AORTA FOR A NOVEL SIGNALING PATHWAY - LEUCINE TO GLUTAMATE

Rat aortic endothelium is differentiated regionally for regulating gua nosine 3',5'-cyclic monophosphate (cGMP) levels in underlying smooth m uscle by signaling via nitric oxide and prostaglandin H-2. Highest act ivity is just distal to the aortic arch and diminishes peripherally. T he same differentiation pattern is reported here for a third and novel signal pathway: endothelial conversion of L-leucine to L-glutamate. S equential segments of rat aorta incubated in vitro convert L-[U-C-14]l eucine to a major C-14 metabolite identified as L-glutamate. Net synth esis of glutamate is greatest in aortic segments of the ''windkessel'' region; significant quantities are also observed in the pancreas, tes tis! and lung but very little in 10 additional tissues. Endothelial ce lls cultured from mouse brain, human umbilical vein, or bovine aorta a nd human peripheral blood macrophages also form [C-14]glutamate. When aortic segments are denuded of endothelium, treatment with L-glutamate in the presence of 3-isobutyl-1-methylxanthine significantly increase s the cGMP content. A number of leucine derivatives inhibit the leucin e-to-glutamate conversion and decrease the cGMP content in aortic segm ents in vitro.