Heme oxygenase immunoreactive neurons in the rat intestine and their relationship to nitrergic neurons

Background: Carbon monoxide (CO), like nitric oxide (NO), is a putative gas eous neurotransmitter. CO is produced by the enzyme heme oxygenase (HO) act ing on a family of heme-containing compounds. Two isomers of HO have been c haracterized (HO-1, HO-2). In the CNS and in peripheral ganglia HO-2 occurs in a majority of neurons. NO and CO function as transmitters of enteric ne urons but the relative distribution of enteric neurons utilizing these gase ous transmitters is unknown in rodent. We have studied the distribution of HO-2 immunoreactivity and NO synthase (NOS) activity within the rat ileum. Methods: Tissue sections and primary neuronal cell cultures were incubated with a HO-2 specific antibody, and then assessed or reprocessed for NOS act ivity using NADPH-dependent diaphorase staining. Results: HO-2 immunoreacti vity was expressed in subpopulations of myenteric and submucosal neurons. A pproximately 45% of the ganglion cells in tissue section were HO-2 positive . This was similar in proportion to those found to stain for NOS activity, and 10% of HO-2 positive neurons also contained NOS. HO-2 immunoreactivity was also found in epithelial cells within the villi, and in interstitial ce lls around the myenteric plexus and within the smooth muscle. In culture, t he distribution and colocalisation of HO-2 and NOS positive neurons was sim ilar to that in tissue sections. We identified labelled neurons as either D ogiel Type I or II; only Type ii cells colocalized NOS and HO-2. Conclusion : Neurons, endocrine-like cells and interstitial cells with the capacity fo r CO production are distributed throughout the ileum and some neurons have the capacity to synthesize both NO and CO as gaseous messengers. (C) 1999 E lsevier Science B.V. All rights reserved.