Rat Monoamine Oxidase Research Articles

Parallel tubular structures in Fc-receptor bearing lymphocytes

H2O2-generating monoamine oxidase can be visualized in the light microscope with tetrazolium, metal salt (ferricyanide) and coupled peroxidatic oxidation methods. Due to methodological draw-backs these procedures do no allow satisfactory results. In search for an alternative method a light microscopic cerium procedure was designed in which the primary reaction product, cerium perhydroxide, serves for the generation of amplified and intensified diaminobenzidine brown. With this cerium-diaminobenzidine-H2O2-Co method monoamine oxidase was visualized more easily and reliably and with higher sensitivity and more precise localization than with the other techniques. At present this method is considered to be the procedure of choice and was used to re-investigate and investigate the distribution of monoamine oxidase in rats, mice, gerbils, guinea-pigs, marmosets, monkeys and man. In these species many cells and tissues showed monoamine oxidase activity where the enzyme has not yet been found before and the structures with already known monoamine oxidase activity showed an improved localization.

SYNTHETIC RATES OF MONOAMINE OXIDASE IN RAT LIVER AFTER CLORGYLINE OR DEPRENYL ADMINISTRATION

SYNTHETIC RATES OF MONOAMINE OXIDASE IN RAT LIVER AFTER CLORGYLINE OR DEPRENYL ADMINISTRATION

Enhanced selectivity of pargyline as an inhibitor of type B monoamine oxidase in harmaline-treated rats

Pargyline, a slightly selective inhibitor of type B monoamine oxidase (MAO), inhibited phenylethylamine oxidation by 88 ± 1% and 81 ± 1% in rat brain and liver, respectively, at 24 hrs after injection of a 30 mg/kg i.p. dose. Serotonin oxidation was inhibited to a lesser extent, 68 ± 4% and 68 ± 2%, respectively, in brain and liver. In rats treated with harmaline, a short-lasting reversible MAO inhibitor selective for type A MAO, the inhibition of phenylethylamine oxidation after pargyline injection still occurred but the inhibition of serotonin oxidation was prevented. These results illustrate that a selective MAO inhibitor can be used to enhance the selectivity of an irreversible inhibitor, presumably by occupying active sites on a certain form of MAO temporarily and thereby preventing its inactivation. In heart, inhibition of both phenylethylamine and serotonin oxidation by pargyline was prevented by harmaline; this finding supports other evidence that phenylethylamine is metabolized by type A MAO in rat heart.

Differential effects of L-thyroxine on cardiac and hepatic monoamine oxidase activity toward benzylamine and serotonin.

Male and female rats of 2 age groups were given subcutaneous injections of L-thyroxine (500 mug/kg) at 12 h intervals for a period of 10 days. The activity of monoamine oxidase (MAO) in normal and thyrotoxic rats was studied with two substrates: benzylamine and serotonin. The results showed that a thyroxine effect on cardiac and liver MAO activity is dependent on the substrate used in the assay. Kinetic studies of cardiac and liver MAO after thyroxine-treatment showed an unaltered Km for benzylamine but a change in Km for serotonin. Both findings may indicate a discriminative action of thyroid hormones on different forms of MAO. The possible presence of a soluble activator and inhibitor for MAO was investigated.

Substrate-selective inhibition of monoamine oxidase by some cyclopropylamino substituted oxadiazoles

1. Inhibition of rat monoamine oxidase by 5-phenyl-3-( N-cyclopropyl) ethylamine-1,2,4-oxadiazole (PCO) has been studied in vitro and in vivo. The compound is an irreversible inhibitor showing selectivity for the serotonin oxidising site (A-site) of the enzyme. 2. Substitution in the 5-phenyl ring of PCO gives compounds which may also be selective for the A-site such as the 2-chlorophenyl compound, may show no selectivity or may, like the 3-nitrophenyl compound, be selective for the B-site of the enzyme. 3. The selectivity found when these inhibitors react with monoamine oxidase in vitro is also apparent when the enzyme from rats which have received single doses of the compounds is studied, but is less clearcut after repeated administration.

Mechanism of action of clenpyrin on the cattle tick Boophilus microplus

AbstractClenpyrin is effective against all stages of development of one‐host cattle ticks (Boophilus spp.) including strains resistant to organophosphorus compounds and carbamates. Ticks treated with clenpyrin are quickly immobilised due to a slackening of the muscles. Manometric measurements revealed a marked depression in respiratory gas exchange and a rise in the R Q within 24 h after treatment. Clenpyrin inhibits NADH oxidation and, as a result, all synthesising processes in the tick. The breakdown of proteins taken up with the blood meal is also inhibited. Clenpyrin, however, does not interfere with carbohydrate degradation. These results have been corroborated in detail by determining various substances in treated and untreated ticks: proteins, haematin, guanine, glycogen, glucose, lactate, ATP, lipoids and cuticular wax. Clenpyrin does not inhibit tick proteinase, tick and other acetylcholinesterase, or rat monoamine oxidase; therefore, the mode of action of clenpyrin differs from that of other known tickicides, especially those involving the acetylcholinesterase system.

Rates of recovery of irreversibly inhibited monoamine oxidases: a measure of enzyme protein turnover.

1. After irreversible inhibition of monoamine oxidase (MAO) in rats with hydrazine derivatives (3-amino-2-oxazolidinone, furazolidone, benmoxine) and the non-hydrazine pargyline, recovery of enzyme activity occurred at rates which were characteristic for the organ investigated and independent of the chemical structure of the irreversible inhibitor. The respective half times were the same in homogenates and in mitochondria and amounted to about 10 days in the brain and 3 to 4 days in the liver; in the small intestine, mucosal MAO activity recovered with a half time of 0.5 days, whereas in the residual intestinal layers a half time of about 4 days was found.\3-Tranylcypromine is not an irreversible inhibitor: the half times of MAO recovery were 3.6 days in the brain and 2.4 days in the liver. Thus, long duration of inhibition and organ-specific half times of recovery of MAO inhibition are characteristic features of irreversible inhibitors. 2. When mitochondrial protein was labelled by i.v. injection of 14C-leucine, specific radioactivity declined with a half time of 9.4 days in the brain and 4.0 days in the liver; for the intestinal mucosa and for the residual intestinal layers, a half time of 0.5 and 4.4 days, respectively, was found. As these values are nearly identical with those found for the rates of MAO recofery after irreversible inhibition, the assumption is supported that irreversibly inhibited MAO must be replaced by newly synthetized enzyme. Vice versa, the rates of MAO recovery after irreversible inhibition seem to reflect the rates of mitochondrial protein turnover. Measurements of the rate of recovery of irreversibly inhibited MAO activity may therefore be useful to determine the turnover of the enzyme protein.