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Biomedical subjects

K Tekes

Publications and source records attributed to K Tekes.

At least 19 recordsLinked to original sources
PubMed2005

Plasma nociceptin levels are reduced in migraine without aura.

It was demonstrated that both nociceptin, a novel opioid neuropeptide, and its receptor are present in trigeminovascular neurons. In an animal model nociceptin dose-dependently inhibited neurogenic dural vasodilatation. These results suggest that nociceptin may be involved in neurovascular headaches such as migraine. To test this hypothesis, we studied circulating nociceptin levels in 18 patients suffering from migraine without aura and in 24 controls. Headache-free migraineurs had significantly lower nociceptin levels than controls (5.79 +/- 1.82 vs. 9.74 +/- 2.43 pg/ml, P < 0.0001, Student's t-tests). Nociceptin levels were further reduced in six patients studied in the first 3 h of typical migraine attacks (1.04 +/- 0.17 pg/ml). Nociceptin levels correlated with the frequency of attacks in this group of migraineurs. Lower interictal nociceptin levels may contribute to a defective regulation of trigeminovascular neurons in migraineurs which might be important in the pain process of migraine.

Adult↗
PubMed2004

Endorphin excess at weaning durably influences sexual activity, uterine estrogen receptor's binding capacity and brain serotonin level of female rats.

Perinatally, the first encounter between the maturing receptor and its target hormone results in hormonal imprinting, which adjusts the binding capacity of the receptor for life. In the presence of an excess of the target hormone or foreign molecules than can be bound by the receptor, faulty imprinting carries life-long consequences. In cytogenic organs, imprinting could also be provoked in other periods of life (late imprinting). Imprinting also durably influences the production of the imprinter and related hormones. In the present study, single beta-endorphin doses was given to three-week old female rats at 3 microg/animal, and the serotonin in five brain regions (frontal cortex, striatum, hippocampus, hypothalamus and brain stem) and uterine estrogen receptor content were determined, thymic glucocorticoid receptor binding capacity was measured, and sexual behavior was tested at five months of age. Brain serotonin levels highly significantly decreased, while sexual activity (Meyerson index and lordosis quotient) increased. At the same time, uterine estrogen receptor affinity decreased. There was no change in receptor binding capacity in the thymus. We will go on to discuss interrelations between the results. The experiments demonstrate that a non-perinatal treatment with a molecule acting at receptor level (late imprinting) can also lastingly influence various indexes in non-cytogenic organs. The results call attention to the possible long-lasting influence of an endorphin surge (caused, for example, by pain) on brain serotonin content and sexual behavior.

Animals↗
PubMed2004

Circulating nociceptin levels during the cluster headache period.

The trigeminal innervation of the dura and its vessels has a prominent role in the mechanism of cluster headache. Nociceptin, an opioid neuropeptide, is the endogenous ligand of the OP-4 receptor, with both algesic and analgesic properties depending on the site of action. Nociceptin and its receptor are expressed by trigeminal ganglion cells where they co-localize with calcitonin gene-related peptide, a marker peptide of the trigeminovascular neurones. Nociceptin inhibits neurogenic dural vasodilatation, a phenomenon related to trigeminovascular activation. To explore its possible involvement in cluster headache, we studied circulating levels of nociceptin when attack-free during the cluster period, and also after the termination of the cluster period, using radioimmunoassay. In 14 cluster headache patients nociceptin levels during the cluster period were significantly lower than in age-, and sex-matched controls (4.91 +/- 1.96 vs. 9.58 +/- 2.57 pg/ml, P < 0.01). After the termination of the cluster period nociceptin levels (8.60 +/- 1.47 pg/ml) were not statistically different from controls. Nociceptin levels did not correlate with age, length of disease or episode length. Lower nociceptin levels during the cluster period may result in a defective regulation of trigeminal activity that might not protect sufficiently against the attacks.

Adult↗
PubMed2001

Protective effect of 7-nitroindazole against DSP-4 induced noradrenaline depletion in mouse hippocampus.

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a selective noradrenaline (NA) uptake blocker, capable of inducing a long-lasting depletion of NA in some noradrenergic axon terminals originating from the locus coeruleus in rodents. Pretreatment with 7-nitroindazole, a fairly selective inhibitor of neuronal nitric oxide synthase in vivo, partially prevented DSP-4 induced NA depletion in mouse hippocampus measured seven days after the neurotoxic insult. Administration of L-arginine, the substrate of nitric oxide synthase, altered neither the NA depletion induced by DSP-4, nor the protective effect of 7-nitroindazole. Inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester did not attenuate the NA depleting effect of DSP-4. Thus, the contribution of neuronal nitric oxide synthase inhibition to the protective effect of 7-nitroindazole needs further studies. As 7-nitroindazole did not block NA uptake, this cannot play a part in the protective effect. The possible contribution of monoamine oxidase B enzyme inhibition by 7-nitroindazole to the protective effect is also discussed.

Animals↗
PubMed2000

Effect of MAO inhibitors on the high-affinity reuptake of biogenic amines in rat subcortical regions.

The noradrenaline (NA), dopamine (DA) and serotonin (5HT) reuptake inhibitory potency of deprenyl, the highly selective and irreversible inhibitor of MAO-B, methamphetamine enantiomers, and some other MAO inhibitors (clorgyline, J-508, J-511, J-512, J-516, LK-63, U-1424, 2-HxMP) was compared. In vitro hypothalamic NA reuptake was inhibited by (+)-, and (-)-methamphetamine, (+)- J-508 and (+)-deprenyl (IC50: 0.35, 3.5, 17.0 and 17.8 mumol/l, respectively), and U-1424, J-512, J-516, LK-63 and 2-Hx-MP showed IC50 > 1000 mumol/l. Striatal DA reuptake was inhibited by (+)-, and (-)-methamphetamine, (+)-, and (-)-deprenyl and clorgyline with IC50 of 0.6, 42.0, 24.0, 98.6 and 27.0 mumol/l, respectively, however the other compounds were ineffective. Hippocampal 5HT reuptake was slightly inhibited by clorgyline (IC50 205.0 mumol/l), while the other MAO-inhibitors were devoid of potency. Data suggest that potency and selectivity of MAO inhibition and reuptake inhibition are independent features of the compounds, and metabolism of deprenyl results in increased noradrenaline and dopamine reuptake inhibition.

Animals↗
PubMed1998

MAO inhibitory side effects of neuroleptics and platelet serotonin content in schizophrenic patients.

In order to study the putative monoamine oxidase (MAO) inhibitory side effect of neuroleptics and simultaneous changes in platelet serotonin content both MAO-B activity and serotonin (5-HT) content in platelets of 30 healthy volunteers and 50 schizophrenic patients treated with neuroleptics were investigated. Our results have shown significantly lower MAO-B activity (15.26 +/- 6.81 S.D. vs. 8.63 +/- 3.82 mmol/hour/10(9) platelets) and higher platelet 5-HT content (906.19 +/- 285.33 vs. 1,727.85 +/- 947.40 ng/10(9) platelets) in the schizophrenic group. Platelet MAO-B activity was considerably lower in paranoid and residual schizophrenics compared with other patients, however, no difference was found in platelet 5-HT content between different subtypes of schizophrenia. Various neuroleptic treatments did not produce different effects either on platelet serotonin content or platelet MAO-B activity.

Antipsychotic Agents↗
PubMed1998

Platelet MAO-B activity and serotonin content in patients with dementia: effect of age, medication, and disease.

This study aimed at determining the effect of drug therapy, age and type of dementia on biological markers. Both platelet monoamine oxidase type B (MAO-B) activity and serotonin content of 57 demented patients and 20 control subjects were determined. Platelet MAO-B activity was measured using [14C]tyramine as substrate. Serotonin content was determined by HPLC-EC method. Increased platelet serotonin content and platelet count was found in patients with dementia compared to controls. A positive correlation was experienced between platelet MAO-B activity, platelet serotonin content and age. Platelet MAO-B activity was higher in the haloperidol treated group, compared with patients treated with anxyolitics. The main original finding of the present study is that platelet serotonin content is increased in demented patients with delusions compared to dementia without complications (p = 0.006). It seems, that platelet MAO-B activity is influenced mainly by drug therapy, while serotonin content rather reflects clinical characteristics in dementia.

Age Factors↗
PubMed1998

Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC) isoenzymes in brain regions of depressed suicides.

The aim of this study was to investigate whether the previously observed adaptive changes in the monoaminergic receptors in post-mortem brains of depressed suicide victims are associated with alteration in some functional proteins involved in serotonergic neuronal signalling, namely PKC and GAP-43. Selected regions from ten brains of antidepressant-free depressed suicide victims and ten matched controls were used to examine the levels of GAP-43 protein, GAP-43 mRNA and PKC isoenzymes by Western blotting with monoclonal antibodies specific for these proteins. A major finding of the study was a significant decrease in GAP-43 protein levels and its mRNA expression in prefrontal cortex (BA9) (by 24% and 34%, respectively) of suicide brains compared to controls. No significant changes were found in GAP-43 protein or its mRNA in frontopolar cortex (BA10), amygdala, substantia nigra or putamen. Levels of PKC isoenzymes had a heterogenous regional distribution but were not significantly altered in any of the regions examined. Given the role of GAP-43 in the establishment and reorganization of synaptic connections, the finding of selective reduction of this protein in prefrontal cortex suggests that a dysfunctional synaptic organization in this region may be associated with depression and suicidal behaviour. This study provides the first evidence of an alteration in a protein related to the neuronal plasticity in the brain of depressed suicide victims.

Adult↗
PubMed1996

The pharmacology of B-type selective monoamine oxidase inhibitors; milestones in (-)-deprenyl research.

(-)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It increases the dopaminergic tone in the central nervous system by a complex mechanism. The MAO-B inhibition could result in a potentiation of the effect and the reduction of the dose of L-dopa, including the restoration of the sensitivity to L-dopa treatment, when the response to the drug has already been diminished or lost. Pre-treatment with (-)-deprenyl prevent the effect of neurotoxins like MPTP, 6-hydroxydopamine, DSP-4, AF64A by inhibiting the conversion of the pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the combination of the two processes. However, other effects of the inhibitor cannot be ruled out. (-)-deprenyl, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells, in a concentration which does not induce MAO-B inhibition. The activity of MAO-B increases with age and the age related changes led to an overproduction of neurotoxic agents. The inhibition of the enzyme activity can play a preventive role against neurodegenerative brain disorders. The most widely used MAO-B inhibitor in the therapy is (-)-deprenyl and it lacks the "cheese reaction". The complex mechanism for the lack of the former effect is not fully known.

Age Factors↗
PubMed1996

Comparison of the vasodilatory effects of bradykinin in isolated dog renal arteries and in buffer-perfused dog kidneys.

This study was undertaken to investigate the role of nitric oxide (NO), cyclooxygenase products and bradykinin (Bk) receptors in the Bk evoked responses of canine renal arteries and perfused kidneys. Rings of isolated canine renal arteries were mounted in organ chambers for measurement of isometric force. The isolated canine kidneys were perfused with Krebs-solution (constant flow) and the perfusion pressure was continuously recorded. The influence of the cyclooxygenase inhibitor indomethacin and the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginin (L-NOARG) on the vasocontractile responses to phenylephrine (PE) were examined in both preparations. Furthermore, the effects of Bk on the tone of canine isolated renal arteries and on the vasopressor responses of isolated buffer-perfused kidneys of dogs were tested in the absence and presence of enzyme inhibitors and the B2 kinin receptor antagonist HOE-140. It was found that indomethacin enhanced the contractile responses of large renal arteries to PE by 77 +/- 10%. In intact artery rings L-NOARG (0.1 mM) caused an additional potentiation of the PE-induced contractions in the presence of indomethacin (from 11.5 +/- 1.2 mN to 21.6 +/- 1.7 mN). However, L-NOARG failed to affect contractile responses to PE in endothelium-denuded rings. Bk produced a concentration-dependent relaxation of the precontracted endothelium-intact renal arteries. The IC50 value for Bk was 11.2 +/- 3.7 nM. The relaxant activity of the peptide in renal artery rings was not affected by indomethacin (3 microM). However, in the presence of L-NOARG a significantly higher concentration (IC50 = 860 +/- 300 nM) of Bk was required to relax renal arteries. The Bk receptor antagonist HOE-140 (10 nM for 40 min) attenuated the relaxant effect of Bk in renal artery rings (from an IC50 of 14.2 +/- 2.5 nM to 216 +/- 37 nM). Indomethacin (3 microM for 20 min) did not significantly alter the arteriolar vasoconstriction (from 45 +/- 4 mm Hg to 48 +/- 5 mm Hg, n = 5) evoked by PE. By contrast, L-NOARG (0.1 mM) potentiated (from 56 +/- 7 mm Hg to 94 +/- 11 mm Hg) the PE-induced vasopressor responses in perfused kidneys. Bk reduced the size of the pressor responses at relatively low concentrations (2-60 nM) but the dose-response curve was flat and the maximum inhibitory effect hardly exceeded 50 percent. Indomethacin (3 microM) did not modify the inhibitory effect of Bk in perfused kidney. In the presence of L-NOARG, Bk depressed the PE induced vasopressor effects with a maximum of 18 +/- 20%. Preincubation of the kidney preparations with the Bk antagonist HOE 140 (10 nM for 40 min) almost completely abolished the inhibitory effect of Bk on the PE induced vasopressor responses. The results suggest that the endothelial NO plays a fundamental role in the relaxant effect of Bk and considerably modulates vascular reactivity to PE in canine renal vasculature. Furthermore, significant difference exists between conduit and resistance vessels of dog's kidney in the effect of indomethacin on the adrenergic contractions.

Adrenergic beta-Antagonists↗
PubMed1996

Platelet rich plasma serotonin content in patients suffering from different psychiatric disorders.

Platelet rich plasma serotonin contents were examined using HPLC-EC method in patients suffering from different anxiety states and compared to age matched healthy controls. We have found significant increase of PRP serotonin level in the group of schizophrenic patients and in patients suffering from dementia compared to controls. PRP serotonin content was significantly lower in heavy drinkers but in patients suffering from panic disorder did not differ significantly from the controls.

Alcoholism↗
PubMed1994

Comparative study of platelet 3H-paroxetine and 3H-imipramine binding in panic disorder patients and healthy controls.

High affinity 3H-paroxetine and 3H-imipramine binding sites were simultaneously studied in platelets of 29 untreated patients with panic disorder and 12 healthy controls. The maximum number of binding sites (Bmax) was found to be significantly lower in the panic patients compared to the controls using either ligand. No difference in the Kd values between the groups of subjects was found. The disturbance of serotonin neurotransmission in panic disorder--decrease in Bmax values--may be either a consequence or a reason of serotonergic dysfunction.

Adult↗
PubMed1993

Further proof that (-)deprenyl fails to facilitate mesolimbic dopaminergic activity.

The selective monaminooxidase (MAO)-B inhibitor (-)deprenyl facilitates the nigrostriatal dopamine (DA)-ergic system by a complex mechanism that includes inhibition of DA reuptake and increase of DA turnover. In this study, DA reuptake and DA turnover were measured in the olfactory tubercle of rats treated with 0.25 mg/kg (-)deprenyl for 28 days. There was no difference between these rats and the saline-treated group. In another series of experiments, we analysed how (-)deprenyl influences the action of some indirectly acting DA agonists, such as amphetamine (AM) and phenylethylamine (PEA). The effect on different behavioural patterns related either to the nigrostriatal (stereotyped behaviour) or the mesolimbic (rearing, locomotion) DAergic system was investigated. As expected, the PEA-induced stereotyped behaviour was tremendously potentiated by (-)deprenyl and the AM-induced stereotypy was reduced. At the same time there was no change in locomotion and rearing. The results give further biochemical and behavioural proof that (-)deprenyl enhances the function of the nigrostriatal DAergic system and leaves the mesolimbic DAergic neurons unaffected.

Amphetamine↗