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Provides information on a study that examined the effects of some drugs with a higher selectivity for the alpha-adrenoceptors on the head-twitch response induced by benzodiazepines, estazolam and triazolam in mice. Methodology of the study; Results and discussion on the study.

Provides information on a study that examined the effect of central noradrenergic neuron system on head-twitch response induced by estazolam, a benzodiazepine derivative in mice. Methodology of the study; Results and discussion on the study.

Presents information on a study which examined the effect of cholinergic drugs on the impairment of avoidance learning induced by thiamine deficiency in mice. Materials and methods; Results; Discussion.

Presents a study that examined the inhibition of rat brain monoamine oxidase (MAO) activity by two analogues of clorgyline. Chemical structures of clorgyline and analogue I and II; Comparison of inhibitory potencies of three compounds tested on MAO-A and MAO-B without and with preincubation; Discussion and conclusion.

Hydrogen atom transfer with a tunneling effect (H-tunneling) has been proposed to be involved in aliphatic hydroxylation reactions catalyzed by cytochrome P450 and synthetic heme complexes as a result of the observation of large hydrogen/deuterium kinetic isotope effects (KIEs). In the present work, we investigate the factors controlling the H-tunneling contribution to the H-transfer process in hydroxylation reaction by examining the kinetics of hydroxylation reactions at the benzylic positions of xanthene and 1,2,3,4-tetrahydronaphthalene by oxoiron(IV) 5,10,15,20-tetramesitylporphyrin π-cation radical complexes ((TMP(+•))Fe(IV)O(L)) under single-turnover conditions. The Arrhenius plots for these hydroxylation reactions of H-isotopomers have upwardly concave profiles. The Arrhenius plots of D-isotopomers, clear isosbestic points, and product analysis rule out the participation of thermally dependent other reaction processes in the concave profiles. These results provide evidence for the involvement of H-tunneling in the rate-limiting H-transfer process. These profiles are simulated using an equation derived from Bell's tunneling model. The temperature dependence of the KIE values (k(H)/k(D)) determined for these reactions indicates that the KIE value increases as the reaction temperature becomes lower, the bond dissociation energy (BDE) of the C-H bond of a substrate becomes higher, and the reactivity of (TMP(+•))Fe(IV)O(L) decreases. In addition, we found correlation of the slope of the ln(k(H)/k(D)) - 1/T plot and the bond strengths of the Fe═O bond of (TMP(+•))Fe(IV)O(L) estimated from resonance Raman spectroscopy. These observations indicate that these factors modulate the extent of the H-tunneling contribution by modulating the ratio of the height and thickness of the reaction barrier.

Two mammalian monoamine oxidases (MAO), MAO-A and MAO-B, are similar in primary structures but have unique substrate/inhibitor selectivities. Carp (Cyprinus carpio) contains a MAO enzyme (C-MAO) with properties different from MAO-A and MAO-B. To determine the molecular characteristics of C-MAO and its phylogenetic relationship with other fish and mammalian MAOs, the primary structure of C-MAO was estimated. The putative C-MAO cDNA encodes 526 amino acids with 59.001 Da, and the deduced amino acid sequence showed as much as 68.9% homology with some mammalian MAO-A proteins, 69.8% homology with some mammalian MAO-B proteins, and as much as 92.4% homology with some fish MAOs. Comparison of two regions in the polypeptide sequence of C-MAO determining possible substrate/inhibitor preferences of MAO-A and MAO-B showed both 79.5% homologies., (2009 Elsevier Inc. All rights reserved.)

We have previously reported that carp (Cyprinus carpio) tissue mitochondria contain a novel form of monoamine oxidase (MAO), which belongs neither to MAO-A nor to MAO-B of the mammalian enzyme. This conclusion results from the findings that the carp MAO was equally sensitive to a selective MAO-A inhibitor clorgyline and to the MAO-B selective inhibitor l-deprenyl, when tyramine, a substrate for both forms, serotonin or beta-phenylethylamine, a substrate for either A or B-form of mammalian MAO, was used. In the present study, we tried to detect another amine oxidase, termed tissue-bound semicarbazide-sensitive amine oxidase (SSAO), activity in carp tissues. As definition of SSAO was used, such as insensitivity to inhibition of the kynuramine oxidizing activity by an MAO inhibitor pargyline and high sensitivity to the SSAO inhibitor semicarbazide. The results indicated that the oxidizing activity was selectively and almost completely inhibited by 0.1 mM pargyline alone or a combination of 0.1 mM pargyline plus 0.1 mM semicarbazide, but not by 0.1 mM semicarbazide alone. We also tried to detect any SSAO activity by changing experimental conditions, such as lower incubation temperature, higher enzyme protein concentration, a lower substrate concentration and different pH's in the reaction, as the enzyme source. However, still no SSAO activity could be detected in the tissues. These results conclusively indicate that carp tissues so far examined do not contain SSAO activity.

To study the molecular structure of guinea pig monoamine oxidase (MAO) and its phylogenetic relationship with other mammalian MAOs, we determined nucleotide sequences of putative MAO cDNAs isolated from guinea pig tissues. Both the 5'- and 3'-ends of the cDNAs were amplified using the RACE (rapid amplification of cDNA ends) method. The sequence (1924 bp) of a putative guinea-pig MAO-B cDNA covers a complete coding region that corresponds to 521 amino acids. We also analyzed a partial sequence of a putative guinea-pig MAO-A cDNA, which corresponds to 506 amino acids, but have left the region of 66 bp at the 3'-end undetermined. The nucleotide and deduced amino-acid sequences of the putative guinea-pig MAO cDNAs showed the highest homology with that of human MAO cDNAs among the known mammalian MAO sequences. These results suggest that guinea-pig MAOs are structurally similar to human MAOs. Our molecular phylogenetic data support the idea that guinea pigs and rodents diverged before the separation between rodents and other lineage leading to Primates and Artiodactyla.

The present study examined whether bisphenol A enhanced 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (*OH) generation in rat striatum using microdialysis technique. These elevations were detected by increases in non-enzymatic formation of 2,3-dihydroxybenzoic acid levels. Bisphenol A significantly enhanced MPP+-induced.OH generation. Further, the effect of diltiazem, a L-type Ca2+ channel antagonist, on bisphenol A (10 microM) and MPP+ (5 mM)-induced.OH generation were studied. Ddiltiazem (100 microM) significantly suppressed bisphenol A and MPP+-induced.OH generation. The results indicate bisphenol A augmented *OH generation, and diltiazem may have preventive effect on bisphenol A and MPP+-induced.OH generation.

The present study examined the ability of antioxidant effects of nicotine on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (*OH) formation of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused through a microdialysis probe to detect the generation of.OH as reflected by non-enzymatic formation trapped as 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP(+) enhanced generation of.OH formation trapped as DHBA. However, nicotine (100 microM) significantly suppressed.OH formation induced by MPP(+). Iron (II) (2, 5 and 10 microM) increased the levels of DHBA in a concentration-dependent manner. However, in the presence of nicotine (100 microM), the effect of nicotine was suppressed. These results suggest that nicotine has a preventive effect on.OH generation by MPP(+) in rat striatum.

Various mammalian tissues contain membrane-bound amine oxidase termed semicarbazide-sensitive amine oxidase (SSAO). A variety of compounds has been identified as relatively selective SSAO inhibitors, but those inhibitors currently available also inhibit monoamine oxidase (MAO). In the present study, inhibitory properties of 2-bromoethylamine (2-BEA) and 3-bromopropylamine (3-BPA) toward rat lung-bound SSAO have been studied. Regardless of preincubation, 2-BEA could not appreciably inhibit MAO-A and MAO-B activity, but 3-BPA at relatively high concentrations inhibited only MAO-B activity. 3-BPA was a competitive and reversible SSAO inhibitor with a Ki value of 17 microM regardless of preincubation. In contrast, without preincubation, 2-BEA competitively inhibited SSAO activity with the Ki value of 2.5 microM and after preincubation, the mode of inhibition changed to be noncompetitive, indicating irreversible inhibition after the preincubation. Dialysis experiments with 2-BEA-pretreated homogenate resulted in no recovery of SSAO activity even after overnight dialysis. A decreased rate of SSAO inhibition under N2 atmosphere to that obtained under O2 was produced upon preincubation of enzyme with 2-BEA, suggesting that oxidized intermediate was necessary for its inhibitory activity. Thus, 2-BEA first interacts with SSAO to form a reversible complex with a subsequent reaction, leading this complex to the covalently bound enzyme-inhibitor adduct. The data analyzed by the plot of 1/k' vs 1/2-BEA concentrations intersected on the y-axis indicate that the inhibition by 2-BEA is not mediated by a bimolecular reaction; thus it is not an affinity-labeling agent, but a suicide SSAO inhibitor. 2-BEA may be employed as a useful compound in the studying SSAO.

Various mammalian tissues contain plasma membrane-bound amine oxidase, termed semicarbazide-sensitive amine oxidase (SSAO). In the present study, 2-bromoethylamine has been studied with regard to inhibitory properties towards tissue-bound SSAO in rat lung. Without preincubation, 2-bromoethylamine was a competitive and reversible SSAO inhibitor with a Ki value of 2.5 microM. After preincubation, it time-dependently and non-competitively inhibited SSAO activity, probably by forming the covalently-bound enzyme-inhibitor adduct. The data presented suggest that 2-bromoethylamine may act as a suicide inhibitor of SSAO.

During 30 days of thiamine deficiency (TD) feeding, the rat antinociceptive effect (pain threshold) to noxious heat stimulation was significantly increased in proportion to the decrease substance P (SP) fluorescent intensity in the spinal cord. Only a single injection of thiamine HCl (0.5 mg/kg, s.c.) on the early treatment day during TD feeding effectively reversed the analgesic effect to the pair-fed control level. Whereas this reversal effect by thiamine treatment was not found if this treatment was done on the relatively late day. However, either treatment day, except muricide, complete disappearance of various animal behaviours induced by TD was found. These results indicate that, after certain degree of TD development, TD-induced behavioral effects might be reversible, but the afferent nerve fibers might be irreversibly damaged, probably by the similar mechanism as found for an excitotoxin(s) mediated injury in the certain brain region(s). The results also suggest a possibility that SP and an excitotoxin, glutamate, in the dorsal part of the spinal cord greatly contribute to the pain transmission induced by noxious heat stimulation.

Ifenprodil, a cerebral vasodilator and non-competitive glutamate antagonist, is also an anti-ischaemic agent; it has been shown to inhibit both forms of MAO in rat brain and lung (with slightly greater potency towards MAO-A), but it does not inhibit SSAO. The effects of ifenprodil on rat brain regional levels of monoamines and their principal metabolites following transient global ischaemia have been investigated 1 h after reperfusion. Among the three most ischaemically vulnerable brain regions (striatum, hippocampus and cortex), striatal DA, DOPAC, HVA, 5-HT and 5-HIAA levels were the most markedly increased. Simultaneous treatment with ifenprodil during reperfusion reversed the increases in the striatum, except for HVA, to the level similar to those of sham-operated controls. In contrast to the striatum, ifenprodil failed to reverse the increases seen in the cortex and hippocampus.

A mechanism of antidepressant activity of beta-amyrin palmitate was studied using the forced swimming method in mice. Beta-amyrin palmitate (10 mg/kg) reduced the increase in the duration of immobility induced by tetrabenazine (100 and 200 mg/kg), but showed no effect on that in mice treated with alpha-methyl-para-tyrosine (500 mg/kg). Beta-amyrin palmitate (5 and 10 mg/kg) decreased the duration of immobility in mice treated with desipramine plus 6-hydroxy-dopamine (50 micrograms/mouse), but did not affect that induced by nomifensine plus 6-hydroxydopamine. The decreased immobility produced by desipramine (15 mg/kg) was not affected by beta-amyrin palmitate. A study of norepinephrine release in mouse brain synaptosomes indicated that beta-amyrin palmitate caused a release of [3H]norepinephrine. The results of the present study suggest that beta-amyrin palmitate might release norepinephrine from newly synthesized pools, and thus, it might activate noradrenergic activity.