Yoshitaka Taguchi

Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decar☐ylase as a marker

The distribution of histidine decarboxylase-like immunoreactivity (HDCI) in the rat central nervous system was studied by the indirect immunofluorescence technique. HDCI cell bodies were concentrated in the posterior hypothalamic area, such as in the tuberal magnocellular nucleus, caudal magnocellular nucleus, posterior hypothalamic nucleus and lateral hypothalamus just lateral to the fasciculus mammillothalamicus at the level of the posterior hypothalamic nucleus. Extensive networks of HDCI fibers of various densities were found in many areas of the brain; they were particularly dense in the hypothalamus but were also found in the following areas: rostrally in the cerebral cortex, olfactory nuclei, medial amygdaloid nucleus, n. tractus diagonalis, and bed nucleus of the stria terminalis, and caudally in the central gray matter of the midbrain and pons, auditory system, n. vestibularis medialis, n. originis nervi facialis, n. parabrachialis, n. commissuralis, n. tractus solitarii, and n. raphe dorsalis.

Evidence for the presence of a histaminergic neuron system in the rat brain: An immunohistochemical analysis

Histamine-containing cells in rats were identified by indirect immunofluorescent histochemistry using an antibody raised against histidine decarboxylase (HDC), the enzyme forming histamine, which was purified from fetal rat liver. HDC-like immunoreactive (HDCI) structures could be detected in the brain as well as in peritoneal mast cells and basal-granulated cells in deep crypts of the gastric mucosa of rats. Numerous HDCI neurons were found in the posterior hypothalamic area and HDCI nerve fibers with a varicose appearance of fluorescence were widely distributed in various regions of the brain.

Effect of α-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, on histamine levels in mouse tissues

Abstract The effects of α-fluoromethylhistidine (α-FMH), a new suicide inhibitor [Kollonitsch et al., Nature, Lond. 274 , 906 (1978)], on histidine decarboxylase (HDC) activities and histamine contents of the skin, fundic stomach and brain of mice were investigated. Four hours after i.p. administration of α-FMH to ddy mice, HDC activities in the brain, stomach and skin had decreased in a dose-dependent way (1–25 mg/kg), by a maximum of 90–95%. The histamine levels in the brain and stomach decreased to 50% of the control levels, whereas the level in the skin did not change at all. The time courses of changes in HDC activities and histamine levels were examined. After i.p. administration of 25 mg/kg of α-FMH, HDC activities in these tissues dropped rapidly within 1 hr. Recovery of HDC activities in the stomach and skin began within 12 hr, but the activity in the brain remained low for 24 hr, confirming the result of Garbarg et al. [ J. Neurochem. 35 , 1045 (1980)]. The histamine content of the stomach decreased to 40% of the original level in 8 hr and recovered within 12 hr, whereas that in the brain decreased to 50% and remained low for more than 24 hr. The histamine content of the skin did not change. These results suggest that the histamine level that was not reduced by α-FMH was derived from mast cells. During the above experiments, no behavioral changes of the animals were detected. α-FMH prevented the increase in HDC activity in mouse kidney on day 18 of gestation when administered i.p. every 12 hr from day 13. No abnormalities were seen in fetuses and neonates after this treatment. It is concluded that α-FMH causes depletion of newly synthesized histamine in situ and, thus, is useful for studies on histamine.

Origins of histamine-containing fibers in the cerebral cortex of rats studied by immunohistochemistry with histidine decar☐ylase as a marker and transection

The origins of histamine-containing fibers in the cerebral cortex were examined by means of the retrograde tracer technique of horseradish peroxidase (HRP)-immunohistochemistry with histidine decarboxylase (HDC) as a marker for the histamine neuron system. Total transection of the brain rostral to the posterior hypothalamus resulted in disappearance of HDC-like immunoreactive (HDCI) fibers in the cerebral cortex, but total transection caudal to the posterior hypothalamus did not decrease the number of HDCI fibers in the cortex, suggesting that HDCI fibers in the cerebral cortex originate in the posterior hypothalamus. The projection of HDCI neurons from the posterior hypothalamus to the cerebral cortex seemed to be bilateral because hemi-transection of the brain rostral to the posterior hypothalamus resulted in a bilateral decrease of HDCI fibers in the cerebral cortex with ipsilateral predominance. After injection of HRP into the cerebral cortex, numerous cells containing both HRP granules and HDCI structures were found bilaterally in the tuberal, caudal and postmamillary magnocellular nuclei, with ipsilateral predominance. These findings indicate that HDCI cells in the above nuclei give rise to axons extending bilaterally to the cerebral cortex.

Increase in histidine decarboxylase activity in mouse skin after application of the tumor promoter tetradecanoylphorbol acetate

Summary A tumor promoter in two-step carcinogenesis, 12-O-tetradecanoylphorbol-13-acetate, was painted on the dorsal skin of C57BL/6 mice. Within 12 hr after a single application of TPA the activity of histidine decarboxylase increased 10 times. The activity of ornithine decarboxylase also increased, but its increase was significantly earlier than that of histidine decarboxylase. Preincubation of a crude extract of the skin with α-fluoromethyl-histidine, a suicide inhibitor of histidine decarboxylase, completely inhibited the increase in histidine decarboxylase activity, indicating the distinct natures of the two decarboxylases.

Effect of α‐Fluoromethylhistidine on the Histamine Content of the Brain of W/Wv Mice Devoid of Mast Cells: Turnover of Brain Histamine

Abstract: In the brains of W/Wv mutant mice that have no mast cells, the histidine decarboxylase (HDC) level is as high as in the brain of congenic normal mice (+/+), but the histamine content is 53% of that of +/+ mice. The effects of a‐fluoromethylhistidine (α‐FMH) on the HDC activity and histamine content of the brain of W/Wr and +/+ mice were examined. In both strains, 30 min after i.p. injection of α‐FMH the HDC activity of the brain had decreased to 10% of that in untreated mice. The histamine content decreased more gradually, and after 6 h about half of the control level remained in +/+ mice, whereas histamine had disappeared almost completely in W/Wv mice. It is concluded that the portion of the histamine content that was depleted by HDC inhibitor in a short time is derived from non‐mast cells, probably neural cells. The half‐life of histamine in the brain of W/Wv mice was estimated from the time‐dependent decrease in the histamine content of the brain after administration of a‐FMH: 48 min in the forebrain, 103 min in the midbrain, and 66 min in the hindbrain.

Characterization of histamine H1-receptors on astrocytes in primary culture: [3H]mepyramine binding studies.

The characteristics of histamine H1-receptors on astrocytes from the cerebral cortex of newborn rats in primary culture were analyzed with a [3H]mepyramine binding assay, and compared with those in the cerebral cortex. The apparent dissociation constant (KD) of [3H]mepyramine binding, the apparent inhibition constants (Ki) of various H1-ligands for [3H]mepyramine binding and the stereoselectivity of d- and l-chlorpheniramine for the inhibition of [3H]mepyramine binding to receptors on cultured astrocytes and to receptors in the brain tissue were very similar, indicating that these receptors are identical. The apparent density of H1-receptors (Bmax) on astrocytes was 262 +/- 60 fmol/mg protein, which was comparable to that in the brain tissue (194 +/- 24 fmol/mg protein). The development of H1-receptors on cultured astrocytes resembled the postnatal development of the receptors in the rat brain. These results suggest that astrocytes could be one of the main targets of the central histaminergic system.

Mechanism of inactivation of mammalian L-histidine decarboxylase by (S)-α-fluoromethylhistidine

Abstract The mechanism of inactivation by (S)-α-fluoromethylhistidine (FMH) of L -histidine decarboxylase (HDC, L -histidine carboxy-lyase, EC 4.1.1.22) purified from whole bodies of fetal rat was studied. FMH inhibited the activities of HDC purified from fetal HDC as well as HDCs from the brain and stomach of adult rats. The activity was not restored by extensive dialysis, indicating that the inhibition was irreversible. The inactivation of HDC was time and concentration dependent and followed pseudo first-order kinetics. L -Histidine, a substrate, protected HDC against inactivation, but D -histidine did not. Apo-HDC was not inactivated by FMH. On labeling of HDC with [3H]FMH, a correlation was found between the extent of incorporation of radioactivity into the enzyme and the degree of inactivation. Two moles of the inhibitor were incorporated into one mole of HDC (108,000 daltons). Experiments with [carboxyl-14C]FMH and [ring 2-14C]FMH showed that decarboxylation was necessary for the inactivation and that one molecule of FMH moiety was incorporated into an HDC monomer during every three decarboxylations of FMH.

Immunohistochemical analysis of the cross-reaction of anti-rat histidine decar☐ylase antibody with guinea-pig DOPA decar☐ylase

L-Histidine decarboxylase [L-histidine carboxylyase, HDC, EC 4.1.1.22] is an enzyme distinct from L-DOPA decarboxylase [L-aromatic amino acid carboxylyase, DDC, EC 4.1.1.28]: the two decarboxylases from fetal rat liver were completely separated from each other by DEAE-cellulose column chromatography and by affinity chromatography with L-carnosine as a ligand. The antibody raised against this HDC inhibited the HDCs from rat and guinea-pig brains very strongly, but their DDCs very weakly. However, in immunofluorescent histochemical studies, the antibody cross-reacted with DDC-like immunoreactive structures, such as chromaffin cells of the adrenal medulla, the raphe nucleus, the substantia nigra, and the locus coeruleus of the brain of guinea-pigs, but not of rats, suggesting that these two decarboxylases share some antigenic structures.

Comparison of histidine decarboxylases from rat stomach and brain with that from whole bodies of rat fetus

Histidine decarboxylases from the stomach and brain of adult rats were purified 380- and 160-fold, respectively, and their properties compared with those of the enzyme from whole bodies of fetal rats (7600-fold purification). The molecular weights (about 90,000) and the apparentKm values forl-histidine (3×10−4M) of the three enzymes were similar. The pI value of the fetal enzyme was 5.0, and that of the brain enzyme was 5.4. Histidine decarboxylase of the stomach showed two peaks of activity corresponding to those of the fetal and brain enzymes (pIs of 5.0 and 5.4) on isoelectric focusing. Anti-fetal-histidine decarboxylase antiserum inhibited the stomach and fetal enzymes extensively, but the brain enzyme only slightly. These results indicate that there are at least two types of histidine decarboxylase in rat tissues.