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L Voog

Publications and source records attributed to L Voog.

11 recordsLinked to original sources

Chronopharmacology of isoprenaline: the effects on rat plasma concentrations of large neutral amino acids depend on time of day for administration.

This investigation was undertaken in order to test our hypothesis, that the endogenous circadian rhythms in large neutral amino acids (LNAAs) in plasma are partly regulated by beta-adrenergic mechanisms. The beta-adrenoceptor agonist isoprenaline, which is known to decrease the concentrations of rat plasma LNAAs, was given at several time-points over a full 24-h period intraperitoneally to rats, which were killed 1 h later. Isoprenaline, administered in the evening, decreased the plasma amino acid concentrations more than it did in the same doses given in the morning. Also the potency of isoprenaline was in this respect higher in the evening than in the morning. This finding, of a time-of-day dependent relationship between the effects of a beta-adrenoceptor agonist and plasma LNAA concentrations, supports our hypothesis, that beta-adrenergic mechanisms are involved in the endogenous regulation of the plasma LNAA rhythms. We suggest that the known endogenous circadian variation in sympathetic activity, which gives rise to a reciprocal rhythm in beta-adrenoceptor responsiveness, could be one factor explaining that part of the circadian rhythm in plasma LNAA concentrations, which is not due to variations in food intake.

Amino Acids

Is rat brain content of large neutral amino acids (LNAAs) a reflection of plasma LNAA concentrations?

Competition between the large neutral amino acids (LNAAs), including the monoamine precursors tyrosine and tryptophan, for the carrier-mediated transport from plasma into the brain is considered the major regulator of brain LNAA content. The plasma ratio of each LNAA to the sum of all LNAAs, previously, in standardized experiments, has proved an excellent predictor of brain LNAA content. To investigate how diurnal variations in plasma LNAAs are reflected in the brain, we have killed rats, in groups of six, every 1 h throughout one 24 h period. The concentration of each LNAA in both plasma and brain varied with time-of-day. Also the total concentration of LNAAs in brain was shown to vary diurnally. Obviously, variations in total brain LNAA concentration cannot be explained by changes in plasma LNAA ratios. Consequently, other factors, contributing to the regulation of the diurnal rhythm in brain LNAA content, must be considered.

Amino Acids

Diurnal rhythms in rat brain large neutral amino acids (LNAAs), monoamines and monoamine metabolites.

To obtain reliable information on the diurnal rhythms in rat brain large neutral amino acid (LNAA) concentrations, animals were killed, in groups of six, every one h throughout one 24 h period. By using such short sampling intervals, it was possible to detect a statistically significant diurnal variation in the whole brain concentration of each LNAA and to give a more detailed description of these diurnal variations than previously presented. Furthermore, the diurnal variations in whole brain concentrations of the precursor amino acids, tyrosine and tryptophan, were compared with corresponding variations in the respective monoamines and their main metabolites. Similar diurnal patterns were demonstrated for tryptophan, serotonin and 5-hydroxyindoleacetic acid. No such correspondence was detected for tyrosine, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid.

Amino Acids

Relationship between plasma and brain large neutral amino acids in rats fed diets with different compositions at different times of the day.

Large neutral amino acids (LNAAs) compete with each other for carrier-mediated transport through the blood-brain barrier into the brain. The relative plasma concentration, expressed as the ratio of each LNAA to the sum of LNAAs, is considered the main regulator of brain LNAA concentrations. In order to investigate the consistency of this assumption throughout a 24-h period, we have compared the relationship of plasma LNAAs to brain LNAAs among groups of rats fed diets containing various amounts of protein (in order to obtain a wide range of plasma LNAA levels) at two different phases of the light/dark cycle (0900 and 2100 hours). The relationship between plasma and brain LNAAs was found to be dependent on both diet and the time of day. Similar plasma amino acid concentrations in the morning and in the evening contrasted with different brain concentrations. Furthermore, previous findings that brain LNAA concentrations are influenced by plasma amino acid concentrations were confirmed.

Administration, Oral

Diurnal rhythm in absolute and relative concentrations of large neutral amino acids in human plasma.

In order to obtain detailed information on the diurnal plasma rhythmicity in those large neutral amino acids (LNAA) which compete with each other for carrier-mediated transport from plasma into the brain, blood samples were collected every hour for 24h from six healthy men, aged 25-50 yr. The well-known diurnal rhythm in the concentration of plasma amino acids was confirmed and is described in greater detail in this paper. These data might be helpful in clinical situations where LNAAs (e.g. L-dopa, alpha-methyldopa and tryptophan) are used as therapeutic agents, since these amino acids compete with endogenous LNAAs for carrier-mediated transport from plasma into the brain. Furthermore, it was found that the amplitude of variation differed between the individual LNAAs. In addition the relationships between them, expressed as ratios of the concentrations of each single LNAA to total LNAA concentration also possess diurnal rhythms, different from those observed in absolute LNAA concentrations. This rhythmicity in relative LNAA concentrations might be of importance for brain function, since altered relationships between LNAAs in plasma might bring about altered concentrations of LNAAs in the brain and consequently, in monoamine synthesis.

Adult

Diurnal rhythms in rat plasma amino acids.

To obtain detailed data on the diurnal rhythm in rat plasma amino acids, groups of rats were killed every two hours during 24 hours and the amino acids in plasma were measured. By using such a short interval between the blood samples, it was possible to reveal differences in rhythmicity between the various amino acids, more detailed than those previously described. Furthermore, it was found that those large neutral amino acids (LNAA) which compete with each other for the carrier mediated transport from plasma into the brain demonstrated different rhythms, whereby also the relation between these competing amino acids varied during the day. This finding might have implications for the transport of the various LNAAs into the brain, and secondarily also for the synthesis of the monoaminergic neurotransmitters in the neurons, for which the LNAAs tyrosine and tryptophan serve as precursors.

Amino Acids

Toluene-induced decrease in rat plasma concentrations of tyrosine and tryptophan.

The organic solvent toluene is demonstrated to cause a decrease in rat plasma concentrations of tyrosine and tryptophan both after intraperitoneal injections and after inhalation. Tyrosine and tryptophan are precursors to neurotransmitters and are transported from plasma into the brain. As the concentrations of these amino acids in plasma could influence the monoamine synthesis in the brain, this phenomenon might be of importance for the pathophysiology behind solvent-induced effects on brain function.

Animals

Plasma concentration of disopyramide given as capsules and controlled release tablets.

Steady state plasma levels and clinical effects of disopyramide have been compared following administration of standard capsules and controlled release (CR) tablets. Nineteen patients (29-70 years) with atrial or ventricular arrhythmias were treated for two weeks with disopyramide capsules 200 mg t.i.d. and then with CR tablets 300 mg b.i.d. for 14 weeks. After treatment either with capsules or CR tablets, plasma concentrations of disopyramide and its metabolite N-deisopropyldisopyramide were similar within 1 dosage interval. Maximum and minimum concentrations of the parent drug were 10.1 +/- 0.9 mumol/l (mean +/- SEM) and 5.7 +/- 0.5 mumol/l with CR tablets, and 10.2 +/- 0.5 mumol/l and 5.6 +/- 0.5 mumol/l with standard capsules. The bioavailability of disopyramide was the same after capsules and CR tablets. Disopyramide, independent of the formulation, produced good antiarrhythmic effects. The side-effects reported on questioning were mainly of the anti-cholinergic type and there was no significant difference between the formulations with respect to their incidence, type or severity. Of 16 patients who stated a preference for one of the dosage forms, 11 prefered the CR tablets. The study confirms the good antiarrhythmic effect of disopyramide and shows that the CR preparation permits twice daily administration of disopyramide.

Adult