Heme oxygenase-2 and nitric oxide synthase immunoreactivity of bovine olfactory receptor neurons and a comparison with the distribution of NADPH-diaphorase staining

It has recently been suggested that, in addition to nitric oxide (NO), carb on monoxide (CO) is an important gaseous messenger which might be involved in vertebrate olfactory transduction because its effects include activation of guanylyl cyclase and the formation of cGMP. As there is no information regarding the presence of heme oxygenase-2 - the constitutive isoform of th e heme oxygenase system - in olfactory neurons of non-rodent species, we ha ve investigated the distribution pattern of heme oxygenase-2 in the olfacto ry epithelium of the bovine, a representative of macrosmatics. Localization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activi ty of the olfactory epithelium was compared with heme oxygenase-2 and NO sy nthase (NOS) immunoreactivities in order to obtain possible hints at functi onal significance. NADPH-d activity was particularly intense in apical dend rites of receptor neurons. It was also found in Bowman glands and intraepit helial duct cells. Less intense, discrete NADPH-d activity was present also at intermediate and basal levels of the olfactory epithelium, correspondin g to the layer of receptor neuron somata and basal cells. While heme oxygen ase-2 activity mainly occured in neuronal perikarya, a very intense NOS imm unoreactivity, exclusively fur the inducible isoform, was detected in the a pical dendrites. Ultrastructurally, NADPH-d histochemistry showed distinct labelling of membranes, in particular of endoplasmic reticulum, mitochondri a and nucleus. The coincident localization of the moderate NADPH-d activity and heme oxygenase-2 immunoreactivity in receptor cell perikarya suggest a functional association between NADPH-cytochrome P450 reductase and heme ox ygenase-2, in contrast, dendritic localization of NADPH-d activity is topic ally and possibly functionally related to the presence of the inducible iso form of NOS. The results suggest that both CO and NO may be generated in bo vine receptor neurons and thus involved in odorant stimulation. Based on im munocytochemical localization of synthesizing enzymes, NO might be regarded as a direct regulator of transduction related processes while CO might act as a modulator of the initial signal.