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Biomedical subjects

J Tuomisto

Publications and source records attributed to J Tuomisto.

At least 127 records · Page 7Linked to original sources
PubMed1983

Ca-dependence of accumulation of monoamines into synaptosomes and its inhibition by copper.

Effects of various concentrations of extracellular Ca on the high affinity uptake of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) as well as the effects of Ca on Cu-induced uptake inhibition were studied by using striatal, cortical and hypothalamic synaptosomes, respectively. The spontaneous release of all three amines from preloaded synaptosomes by Cu increased slightly with increasing external Ca up to 2.5 mM. The sensitivity to Ca of the accumulation of the amines into synaptosomes decreased in the order of DA greater than NA greater than 5-HT. Below 0.3 mM Ca, DA uptake increased due to concurrent decreased release of DA from synaptosomes. The pattern was similar but less evident for NA while 5-HT uptake and its spontaneous release did not change upon buffer Ca at all. The uptake inhibition of none of the amines depended on extracellular Ca. Zn reversed the Cu-induced inhibition of 5-HT uptake but increased additively the inhibition of DA uptake and that of NA uptake in vitro. The potency of Cu to inhibit uptake decreased when the protein concentration in the incubation medium was increased. Cysteine, added concurrently with Cu, did not protect uptake from the toxic influence of Cu. The results so far suggest that the primary mechanism in the Cu-induced inhibition of uptake is blocking the membrane uptake carrier. The release of an accumulated amine from synaptosomes may rather be secondary and result from the inhibition of the reuptake.

Animals↗
PubMed1983

Dopamine and 5-HT uptake by synaptosomes after pretreatment with p-chlorophenylalanine.

5-Hydroxytryptamine (5-HT) and dopamine uptake were studied in rat hypothalamic and striatal synaptosomes, respectively, after a single-dose or repeated doses of p-chlorophenylalanine (PCPA), and after withdrawal of the drug. 5-HT uptake did not change 24 h after a single large dose of PCPA (300 mg/kg). Uptake of neither amine changed 12 h or 7 days after treatment with 300 mg/kg PCPA every third day, for 2 weeks. In all cases, the kinetic parameters remained identical. These results indicate that depletion of 5-HT levels by PCPA and the resulting decrease in serotoninergic activity do not induce changes in 5-HT or dopamine uptake. Hence, reported changes in transmitter uptake due to clinical or experimental manipulations must not be directly related to synaptic activity.

Animals↗
PubMed1983

Influence of the hormonal balance of late pregnancy on the active uptake of 5-hydroxytryptamine by human blood platelets.

The active uptake of 5-hydroxytryptamine (5-HT) was studied in vitro in the blood platelets of twelve pregnant women during their final two months of pregnancy. The control group consisted of twelve women who were, on average, four days post partum. No significant difference in the uptake of 5-HT by blood platelets was found between these groups. Thus, the rapid fall in blood estrogen and progesterone concentrations after parturition did not seem to influence the uptake of 5-HT in human blood platelets.

Adult↗
PubMed1982

Diurnal variations in brain and pituitary histamine and histamine-N-methyltransferase in the rat and guinea pig.

The circadian variation of histamine concentrations and histamine-N-methyltransferase (E.C. 2.1.1.8., HNMT) activities were measured in different parts of rat and guinea pig brain and pituitary glands after an adaptation to a daily 12-hour light and 12-hour dark schedule. A significantly higher histamine content was found in rat hypothalamus at 19.00 hours, at the end of the light period, then a decline during the dark hours followed by an increase during the daytime. No similar changes were seen either in the other parts of the brain or in the pituitary gland. In the guinea pig hypothalamus a somewhat reverse pattern of histamine content was seen as compared to that in the rat, the peak occurred at 8.00 hours and the lowest level at 14.00 hours. In other parts of the brain the changes were not significant. In rat hypothalamus there were also significant changes in HNMT activities, with a higher level during darkness. In the guinea pig, the HNMT activities were much higher than in the rat, and in hypothalamus, cortex and striatum there was a modest increase at 2.00 hours, with another upward trend at 14.00 hours. It will be of interest to see whether or not these species differences reflect different circadian activity rhythms and/or different living habits of these two species, and with which physiological functions they may be connected.

Animals↗
PubMed1981

Further evidence of the dual role of noradrenaline in regulation of thyrotrophin secretion in male rats.

The dual role previously suggested for noradrenergic neurons in TRH-TSH regulation was studied in male rats. Alpha-Methyl-p-tyrosine (alpha MPT) significantly decreased brain noradrenaline (NA) and dopamine (DA) levels 0.5-6 h after the injection. Maximum inhibition of TSH cold-response occurred at 4 h. One h after administration of L-dopa the brain DA (but not NA) level was considerably elevated. TSH cold-response was not significantly changed. The effects of alpha MPT and Ca-fusarate on the cold-induced TSH secretion were antagonized by neither dihydroxyphenylserine (DOPS; this drug restores NA stores) nor by L-dopa (which restores DA levels). DOPS even potentiated the depressive effect of alpha MPT and Ca-fusarate. When given into the third ventricle, NA did not modify basal TSH levels but decreased the cold-induced TSH secretion. When infused directly into the median eminence of the medial basal hypothalamus, NA reduced both basal and cold-induced TSH secretion. Pinealectomy decreased the TSH cold-response but NA seemed to retain its ability to inhibit TSH secretion. These results demonstrate that besides the possible stimulatory action on TSH secretion, noradrenergic neurons also have an inhibitory effect outside the blood-brain barrier, possibly in the median eminence.

Animals↗
PubMed1980

Nature of lowered 5-hydroxytryptamine uptake by blood platelets of patients with Down's syndrome.

Disturbance of central serotoninergic system has been suggested in Down's syndrome (DS). In this syndrome the 5-HT concentration in blood platelets is below normal, but the mechanism behind this has been controversial. Recently, evidence has accumulated indicating a decreased active transport of 5-HT possibly due to lowered activity of Mg++-dependent Na+-K+-stimulated adenosine triphosphatase. In the present study the kinetic analysis of 5-HT uptake by blood platelets from DS patients revealed a decreased Vmax, suggesting decreased transport function but an unchanged affinity to the uptake receptors, as indicated by normal Km values. The controls were mentally retarded patients from the same institute. The uptake continued in a linear fashion up to 20 min., suggesting an unchanged storage of 5-HT. Also the effect of zinc on the 5-HT uptake was studied; plasma zinc levels have been noted to be lowered in DS infants. In vitro zinc caused a dose-dependent inhibition of uptake at 10(-5) and 10(-4) M. In vivo, after 2 weeks treatment 135 mg/day orally no significant effect was noted.

Adolescent↗
PubMed1980

Tetrahydro-beta-carbolines and corresponding tryptamines: In vitro inhibition of serotonin, dopamine and noradrenaline uptake in rat brain synaptosomes.

The structure activity relationships of tryptolines and some other beta-carbolines and tryptamines as inhibitors of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) uptake were studied in rat brain synaptosomes. All beta-carbolines inhibited to higher degree the uptake of 5-HT than that of DA or NA(IC50's 5-100 times lower). The most potent tryptoline derivative was 6-hydroxy-tetrahydro-beta-carboline (5-hydroxytryptoline, 6-OH-THBC) with an IC50 of 5.0 x 10(-7) M at a 5-HT concentration of 10(-7) M. 6-Methoxy-tetrahydro-beta-carboline (5-methoxytryptoline) was slightly weaker; the inhibition of 5-HT uptake and DA uptake being competitive. Also tetrahydro-beta-carboline (tryptoline) was more potent than its 1-methylderivative, tetrahydroharmane (methtryptoline) or norharmane (beta-carboline). All of them were, however, weaker inhibitors of 5-HT uptake than the freely rotating indoleamines N-methyl-tryptamine (N-Me-T) or 5-HT itself. N-Me-T and 5-HT were also more potent inhibitors of DA and NA uptake than most of the beta-carbolines, DA uptake, however, was inhibited better by 6-OH-THBC than by 5-HT or N-ME-T. Tetrahydro-beta-carbolines may inhibit 5-HT uptake also in vivo but is unlikely that catecholamine uptake is affected.

Animals↗
PubMed1980

Tetrahydro-beta-carbolines and corresponding tryptamines: In vitro inhibition of serotonin and dopamine uptake by human blood platelets.

Tetrahydro-beta-carbolines (THBCs), 6-methoxyharmalan and norharman and the corresponding open chain tryptamines studied inhibited t-hydroxytrypere better inhibitors of DA than 5-HT uptake but THBCs generally were far more potent inhibitors of 5-HT uptake than of DA uptake. 6-methoxy-1,2,3,4-tetrahydro-beta-carboline was as potent as 5-HT itself 3H-5-HT uptake inhibition in platelets and the inhibition was competitive. All the beta-carbolines studied were more potent inhibitors of 3h-da uptake than DA itself. Contrary to results in rat brain synaptosomes, THBCs were more potent in platelets than the corresponding tryptamines with the freely rotating ethylamine side chain. Unsaturated beta-carbolines were weaker inhibitors than THBCs. The clear difference in the rank order of potencies of these compounds in human platelets and rat brain synaptosomes demonstrates that these different model systems for amine uptake studies do not always give comparable results. The results also suggest that there are differences in the uptake systems for 5-HT and DA in human platelets.

Blood Platelets↗
PubMed1980

Effects of histamine and histamine antagonists on the uptake and release of catecholamines and 5-HT in brain synaptosomes.

The effect of histamine and histamine antagonists on the uptake and release of monoamines was studied using rat brain synaptosomes. For uptake experiments, P2-synaptosome fractions were incubated in buffer for 2 min in the presence of tritiated dopamine, noradrenaline or 5-hydroxytryptamine (5-HT) and the inhibitor studied. Only an /H1-antagonist mepyramine (pyrilamine) inhibited monoamine uptake at reasonable concentrations. For release experiments, preloaded synaptosomes were incubated with the substanances to be studied for 2 or 5 min in buffer, and the decrease in radio-activity assayed and compared with synaptosomes incubated with the solvent. Only histamine caused some release, but the concentration range necessary to cause a similar level of release was at least one hundred times greater than that of tyramine. Hence it is unlikely that H2-antagonists would exert their pharmacological effects in the central nervous system by inhibiting monoamine uptake or by causing a tyramine-like releasing effect. Also histamine is necessary at very high concentrations before such secondary effects are likely.

Animals↗
PubMed1979

Decreased uptake of 5-hydroxytryptamine in blood platelets from patients with endogenous depression.

5-Hydroxytryptamine (5-HT) uptake was studied by using blood platelets from 13 patients with endogenous depression (Hamilton rating scale 33 +/- 7) and 13 healthy volunteers. An improved method with a short incubation time and low substrate concentration was used, and the incubation was performed in Krebs-Henseleit buffer (pH 7.4) at 37 degrees C. A clear difference in 5-HT uptake by blood platelets was noted: The Vmax of the reaction in patients was 39, and in controls 71 pmol per 2 x 10(7) platelets in 5 min. There was no significant difference in the Km. After a 4-week treatment with imipramine, a competitive inhibition of 5-HT uptake with an increased Km was seen; after a similar treatment with amoxapine there was little change in 5-HT uptake. Amoxapine was inferior to imipramine as an inhibitor of 5-HT uptake, also in vitro. There was no difference in clinical recovery in these treatment groups. These results may be of importance so as to understand the potential biological differences between depressed patients and normal persons.

Adult↗
PubMed1979

Dual action of adrenergic system on the regulation of thyrotrophin secretion in the male rat.

The effect of graded doses of drugs modifying adrenergic activity on basal and cold-stimulated TSH secretion was studied in male rats. alpha-methyl-p-tyrosine (aMPT) (16 h before 30 min cold-exposure), phenoxybenzamine (1 h), Ca-fusarate (1 h) and diethyldithiocarbamate (DDC) (1 and 18 h) dose-dependently depressed the cold-stimulated TSH secretion. The effect of reserpine (24 h) was not significant. Clonidine (1 h), dihydroxyphenyl-serine (DOPS) (1 h), noradrenaline (NA) (1 h), and L-Dopa (1 h) were also effective in decreasing serum TSH levels, but dopamine (DA) (ad 2 mg/kg, 1 h) had no effect. Basal TSH levels were also decreased by various doses of clonidine, DOPS and NA, given ip 1 h before sacrifice. Clonidine (1 mg/kg), NA (1 mg/kg), DA (2 mg/kg), aMPT (300 mg/kg), phenoxybenzamine (2 or 20 mg/kg), Ca-fusarate (50 mg/kg) or L-Dopa (200 mg/kg) did not modify the TRH-induced TSH response. These results cannot be explained by assuming only a stimulatory function for the adrenergic system on the secretion of TSH in the rat. The site of the possible inhibitory function of noradrenaline in the control of TSH cannot be deduced from these results, but various possibilities are discussed.

Animals↗