TARGETED GENE DELETION OF HEME OXYGENASE-2 REVEALS NEURAL ROLE FOR CARBON-MONOXIDE

Neuronal nitric oxide synthase (nNOS) generates NO in neurons, and hem e-oxygenase-2 (HO-2) synthesizes carbon monoxide (GO). We have evaluat ed the roles of NO and CO in intestinal neurotransmission using mice w ith targeted deletions of nNOS or HO-2, Immunohistochemical analysis d emonstrated colocalization of nNOS and HO-2 in myenteric ganglia, Nona drenergic noncholinergic relaxation and cyclic guanosine 3',5' monopho sphate elevations evoked by electrical field stimulation were diminish ed markedly in both nNOS(Delta/Delta) and HO-2(Delta/Delta) mice, In w ild-type mice, NOS inhibitors and HO inhibitors partially inhibited no nadrenergic noncholinergic relaxation. In nNOS(Delta/Delta) animals, N OS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Delta/Delta) animals.