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Biomedical subjects

C J Fowler

Publications and source records attributed to C J Fowler.

At least 271 records · Page 15Linked to original sources
PubMed1982

The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline.

The kinetics of inhibition of rat liver mitochondrial monoamine oxidase by clorgyline, l-deprenyl and pargyline are consistent with a mechanism whereby a reversible interaction between the inhibitor and the enzyme active site under conditions of thermodynamic equilibrium is followed by a time-dependent formation of the covalently-bound enzyme-inhibitor adduct. The Ki value for the reversible interaction between clorgyline and monoamine oxidase A is about 1000 times lower than that towards the B-form of the enzyme, and this difference is sufficient to account for most, but not all, of the selectivity of the inhibition caused by this compound. The Ki value of the monoamine oxidase B selective inhibitor l-deprenyl towards that form of the enzyme is only about 40-fold lower than that towards the A-form. However, in this case, the rate of formation of the irreversible adduct is considerably faster for the B-form than for the A-form and this makes a major contribution to the selectivity of this compound. Pargyline shows a Ki value towards monoamine oxidase B that is only 8 times lower than that towards the A-form and in this case the rates of formation of the enzyme-inhibitor adducts are similar. The significance of these results are discussed in terms of the selective inhibition of monoamine oxidase.

Animals↗
PubMed1982

Some properties of monoamine oxidase and a semicarbazide sensitive amine oxidase capable of the deamination of 5-hydroxytryptamine from porcine dental pulp.

The deamination of 5-hydroxytryptamine, tryptamine and benzylamine by porcine dental pulp membrane preparations is brought about not only by monoamine oxidase, but also by a clorgyline (and deprenyl) resistant), semicarbazide sensitive enzyme. The semicarbazide sensitive enzyme was also inhibited by aminoguanidine, hydroxylamine and phenylhydrazine, but was not affected to any significant extent by incubation at 50 degrees for up to 100 min. There was, on the other hand, considerable inhibition of monoamine oxidase activity after incubation at this temperature. The semicarbazide sensitive enzyme neither metabolised, nor was inhibited by putrescine or cadaverine. Mixed substrate experiments indicated that 5-hydroxytryptamine and tryptamine interacted at the same catalytic centre on the semicarbazide sensitive enzyme.

Amine Oxidase (Copper-Containing)↗
PubMed1982

Time-dependent inhibition of monoamine oxidase by beta-phenethylamine.

Several reports have suggested that monoamine oxidase activity towards beta-phenethylamine is inhibited by high concentrations of that substrate. This inhibition is not found if initial velocities are measured, but there is a slower time-dependent inhibition at higher beta-phenethylamine concentrations. Such time-dependent inhibition is not found with tyramine as substrate or upon incubation of the enzyme with the reversible inhibitor amphetamine. The inhibition is not due to the accumulation of phenacetaldehyde, phenylethanol or phenacetic acid, or to a reaction of any of these three products either with each other or with beta-phenethylamine. Although the inhibition is time-dependent, the inactivated enzyme slowly regains activity upon removal of the beta-phenethylamine. A model is proposed to explain the observed inhibition.

Animals↗
PubMed1982

The binding of [3H]-5-hydroxytryptamine to homogenates of human brain.

The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT) to homogenates of human brain has been studied. The specific binding is saturable, with a Kd (frontal cortex) of 12 /+- 2 nM, and is inhibited by non-radioactive 5-HT (IC50=26 nM) and D-Lysergic acid diethylamide (IC50=20 nM). Specific, but not non-specific binding of [3H]-5-TH was inhibited by incubation of the homogenates at 50 degrees C. The binding of [3H]-5-HT across the human brain was not uniform, the highest binding being found in the substantia nigra and hippocampus, and the lowest in the thalamus and pons. The Kd of the binding sites towards 5-HT did, however, appear to be similar for the different brain regions.

Animals↗
PubMed1982

Changes in peripheral nerve fibres distal to a constriction.

Continued constriction of the tibial nerve of the rabbit by a ligature was accompanied by a reduction in maximal motor conduction velocity distal to the ligature, and by a reduction in axonal and total fibre diameter. From the presence of paranodal demyelination and distal fibre degeneration in severely affected nerves, it is suggested that in some instances the change in axonal calibre was part of a progressive distal atrophy which could lead to secondary demyelination and ultimately to "dying-back" of the affected axons.

Animals↗
PubMed1982

Metabolism of monoamines in malignant hyperthermia-susceptible pigs.

A comparison of monoamine oxidase activities in the hypothalamus and striatum between malignant hyperthermia-susceptible (Pietrain) and malignant hyperthermia-resistant (Landrace/Large White) pigs showed no significant difference between the two breeds. The concentrations of noradrenaline, dopamine and their non-O-methylated metabolites did not reflect the low activities of monoamine oxidase type A differentially. The malignant hyperthermia-susceptible pigs had significantly greater concentrations of 3,4-dihydroxyphenyl glycol in the striatum, and of 3,4-dihydroxymandelic acid in the hypothalamus. Consequently, in the brain, low monoamine oxidase type A activity does not appear to be involved in susceptibility to malignant hyperthermia. In addition, monoamine oxidase activities in the heart, liver, kidney and intestinal mucosa and catechol-O-methyl transferase activities in the kidney were the same in the susceptible and resistant pigs.

Amines↗
PubMed1982

Deamination of 5-hydroxytryptamine by both forms of monoamine oxidase in the rat brain.

Km and Vmax values of monoamine oxidase (MAO) A and B towards 5-hydroxytryptamine were determined for rat brain homogenates after the in vitro inhibition of one of the two forms by the selective inhibitors clorgyline and l-deprenyl. Km values of 178 and 1170 microM, and Vmax values of 0.73 and 0.09 nmol . mg protein-1 . min-1 towards 5-hydroxytryptamine were found for MAO-A and -B, respectively. The Ki for 5-hydroxytryptamine as a competitive inhibitor of beta-phenethylamine oxidation by MAO-B was found to be 1400 microM. The significance of these findings is discussed.

Animals↗
PubMed1982

Tremor after head injury and its treatment by stereotaxic surgery.

Tremor, both postural and kinetic may be a late complication for victims of severe closed head injury, especially in the young, and may add to their disability. The nature of the tremor is described in eight patients. In each a stereotaxic thalamotomy was performed, dramatically relieving or reducing the severity of tremor in each instance, and resulting in improved function of the affected limb and increased independence. The site of the responsible lesion, which is thought to lie in the mid brain, is discussed together with the indications and contraindications for surgical management.

Adolescent↗
PubMed1981

The activities of monoamine oxidase-A and -B, succinate dehydrogenase and acid phosphatase in the rat brain after hemitransection.

The activities of monoamine oxidase-A and -B were determined in four brain regions (limbic system, occipito-temporal cortex, hemispheres and striatum) of the rat 0, 3, 6, 9 and 14 days after hemitransection of the left side. No larger or consistent change in the activity of monoamine oxidase-A towards 5-hydroxytryptamine was found for the left (hemitransected) side with respect to the right side for any of the rats. The monoamine oxidase-B activity towards beta-phenethylamine increased in the left side striatum to a significant level by 3 days, and in the hemispheres and occipito-temporal cortex on the left side, with respect to the right side by 9 days, but no significant changes were found for the limbic system. A small decrease in the activity of succinate dehydrogenase was found in the striatum on the left side by 9 days after hemitransection, but no change in the activity of acid phosphatase was found in this brain region.

Acid Phosphatase↗
PubMed1981

Monoamine oxidase-A and -B activities in the brain stem of schizophrenics and non-schizophrenic psychotics.

In the pons of autopsy cases who had suffered from chronic schizophrenic or nonschizophrenic psychoses, an increased activity of monoamine oxidase -B but not -A was found, as compared with age-matched controls. Consequently, the ratio of the activities of MAO-B : MAO-A was elevated in the cases of psychosis. There was no significant difference in enzyme activities between schizophrenic and nonschizophrenic psychoses. Lobotomy appeared not to influence the monoamine oxidase activity. Increased ratios of the activities of MAO-B : MAO-A in various brain parts of chronic schizophrenics in comparison with age-matched controls was found in the previously published data of Eckert et al (1980) and Schwartz et al. (1974) but not Crow et al. (1979). The mechanism underlying the change in enzyme activities is unclear. There seems to exist an association between an increased monoamine oxidase-B activity and degenerative processes in the brain resulting in loss of neuronal activity. The change observed may be linked either to pathological processes associated with chronic psychosis or to long-term treatment with neuroleptic drugs.

Adult↗