No abstract

Monoamine oxidases (MAO; EC 1.4.3.4.) A and B occur in the outer mitochondrial membrane and oxidize a number of important biogenic and xenobiotic amines. Monoclonal antibodies specific for human MAO A or B and immunocytochemical techniques were used to visualize the respective enzymes in human placenta, platelets, lymphocytes, liver, brain, and a human hepatoma cell line. MAO A was observed in the syncytiotrophoblast layer of term placenta, liver, and a subset of neurons in brain, but was not observed in platelets or lymphocytes, which are known to lack type A enzyme. MAO B was observed in platelets, lymphocytes, and liver, but not in placenta, which contains little or no MAO B. MAO B was also observed in a subset of neurons in the brain that was distinct from that which contained MAO A. MAO A and MAO B were also observed in some glia. Unlike most tissues examined, liver cells appeared to contain both forms of the enzyme. These studies show that MAO A and MAO B can be specifically visualized by immunocytochemical means in a variety of human cells and tissues and can provide a graphic demonstration of the high degree of cell specificity of expression of the two forms of the enzyme.

Among fifteen male skin fibroblast cultures from eleven donors ranging in age from less than 1 year to 90 years old, the specific activity of monoamine oxidase A (MAO-A) differed 515-fold. Each culture had one of the two most common alleles (three or four 30-bp repeats) at the variable number tandem repeat locus positioned 1.2 kb upstream from MAOA exon 1 (uVNTR). The mean MAO-A activity in cultures with three uVNTR repeats was significantly lower than that in cultures with four repeats (1.6 +/- 1.1 and 13 +/- 12 nmol/h per milligram, respectively; P=0.032). MAO-A expression was confined to a cell sub-population varying from 0.5% to 90% of cells in different cultures. The mean specific activity in MAO-A+ cells (whole culture specific activity divided by the proportion of immunopositive cells) was lower for cultures with three repeats than for those with four (7.2 +/- 3.1 and 23.9 +/- 9.5 nmol/h per milligram protein, respectively; P=0.0013), with no overlap in activity between genotypes. Finding lower MAO-A activity in cultures with three uVNTR repeats compared to those with four is consistent with published evidence that MAO-A promoter constructs bearing three repeats have lower transcriptional activity in transfected neuroblastoma and choriocarcinoma cells. The uVNTR genotype may be a common genetic determinant of significant individual differences in oxidizing capacity for critical MAO-A substrates, which include serotonin, norepinephrine, and tyramine.

Clin. Invest. 1995.95:1169-1173

It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t-MHA may also occur within HA terminals and glial cells.