BRAIN HEME OXYGENASE ISOENZYMES AND NITRIC-OXIDE SYNTHASE ARE CO-LOCALIZED IN SELECT NEURONS

Two isoforms of the enzyme heme oxygenase are expressed in distinct po pulations of neurons in the brain. These enzymes catalyse the oxidativ e cleavage of heme to the cellular antioxidant biliverdin resulting in the release of carbon monoxide in the process. Both heme and carbon m onoxide may play important roles in regulating the nitric oxide-cyclic guanosine monophosphate signal transduction system. Thus we have exam ined the distributions of both isoforms of heme oxygenase in the rat b rain, and compared their localizations with that of nitric oxide synth ase determined with the NADPH-diaphorase histochemical technique. Heme oxygenase-1 is highly expressed in a few select populations of neuron s including cells in the hilus of the dentate gyrus, in the hypothalam us, cerebellum and brainstem. This enzyme appears to be coexpressed wi th nitric oxide synthase only in a few cells in the dentate gyrus. Hem e oxygenase-2 is much more widely expressed. It is present in mitral c ells in the olfactory bulb, pyramidal cells in the cortex and hippocam pus, granule cells in the dentate gyrus, many neurons in the thalamus, hypothalamus, cerebellum and caudal brainstem. However, only some of these labelled neurons also displayed nitric oxide synthase. Instead, many neurons expressing heme oxygenase-2 correspond to those known to express high levels of the hemoprotein soluble guanylyl cyclase. These results suggest that heme oxygenase may play a role in modulating gua nylyl cyclase independent of nitric oxide synthase. This may result fr om regulation of intracellular heme and carbon monoxide levels by the heme oxygenase system.