This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethidine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge.

• MeSH
• alfa-2-adrenergní receptory - antagonisté farmakologie   MeSH
• alfa-2-adrenergní receptory fyziologie   MeSH
• hemodynamika účinky léků   fyziologie   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• náhodné rozdělení MeSH
• nízká teplota škodlivé účinky   MeSH
• potkani Sprague-Dawley MeSH
• srdeční frekvence účinky léků   fyziologie   MeSH
• telemetrie metody   MeSH
• vazokonstrikce účinky léků   fyziologie   MeSH
• yohimbin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The results of linkage and candidate gene association studies have led to a range of hypotheses about the pathogenesis of schizophrenia. We limited our study to polymorphisms in candidate genes involved in dopaminergic and noradrenergic systems, and in the 25KDa synaptosomal-associated protein (SNAP-25) gene that is related to neurotransmitter exocytosis. Eight single nucleotide polymorphisms (SNPs) in regulating or coding regions of genes for the alpha-2A adrenergic receptor (ADRA2A), dopamine receptors D1 and D3 (DRD1 and DRD3), dopamine β-hydroxylase (DBH) and SNAP-25 were genotyped in male patients with schizophrenia (n=192) and in healthy controls (n=213). These polymorphisms were previously associated with schizophrenia. The allelic association between schizophrenia and ADRA2A rs1800544 polymorphism, SNAP-25 rs1503112 polymorphism, and DRD3 rs6280 polymorphism was found in our study. However, only observations for rs1503112 survived correction for multiple testing. Association was also evaluated by considering the polymorphisms as interactions; in this case, a likelihood ratio test (LRT) revealed evidence for association with schizophrenia in four polymorphism combinations: two DRD3*SNAP-25 combinations (rs6280*rs3746544 and rs6280*rs3746544, P=0.02), one ADRA2A*SNAP25 combination (rs1800544*rs3746544) and one ADRA2A*DBH combination (rs1800544*rs2519152). Our results are in agreement with the previously proposed role of DNA polymorphisms involved in dopaminergic, noradrenergic and synaptic functions in the pathogenesis of schizophrenia. Further relevant studies including larger sample size and more markers are needed to confirm our results.

• MeSH
• alfa-2-adrenergní receptory genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• pravděpodobnostní funkce MeSH
• protein 25 asociovaný se synaptozómy genetika   MeSH
• receptory dopaminu D3 genetika   MeSH
• schizofrenie genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Increasing evidences support the importance of epigenetic control in schizophrenia pathogenesis. One of the enzymes involved in DNA methylation process through homocysteine metabolism is methylenetetrahydrofolate reductase (MTHFR). The most extensively studied variant in the MTHFR gene is the C677T polymorphism, resulting in reduced enzyme activity and elevated homocysteine level. METHODS: In sample of 192 schizophrenics and 213 healthy controls an increasing risk of schizophrenia associated with MTHFR 677 CT+TT genotype was found (OR=1.6, p=0.021). Association was also evaluated by considering the C677T polymorphism as an interaction with COMT Val158Met and ADRA2A C-1291G polymorphisms previously associated with schizophrenia risk using a logistic regression analysis. RESULTS: Previous studies of MTHFR*COMT (C677T*Val158Met) interaction in relation to schizophrenia resulted in inconsistent results. In our sample this interaction did not significantly differ between schizophrenics and control subjects. On the other hand analysis of MTHFR*ADRA2A (C677T*C-1291G) interaction revealed significant association between ADRA2A CC+CG genotype in the MTHFR TC+TT carriers (p=0.008). CONCLUSIONS: Our results support role of noradrenergic functions as well as previously proposed role of epigenetic control in the pathogenesis of schizophrenia. Further relevant studies including larger sample size and more markers are needed to prove our results.

• MeSH
• alfa-2-adrenergní receptory genetika   MeSH
• dospělí MeSH
• epigeneze genetická genetika   MeSH
• genetická predispozice k nemoci epidemiologie   genetika   MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• methylentetrahydrofolátreduktasa (NADPH2) genetika   MeSH
• mladý dospělý MeSH
• polymorfismus genetický MeSH
• rizikové faktory MeSH
• schizofrenie epidemiologie   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and alpha-adrenoceptor agonists. We tested the hypothesis that alpha(1)- and alpha(2)-adrenoceptors interact to enhance adrenergic reactivity of mesenteric veins. We studied neurogenic and agonist-induced constrictions of mesenteric veins and arteries in vitro. Norepinephrine concentration-response curves were left-shifted in veins compared to arteries. UK 14,304 (0.01-1 microM, alpha(2)-adrenoceptor receptor agonist) did not constrict arteries or veins but enhanced constrictions and Ca(2+) signals mediated by alpha(1)-adrenoceptor stimulation in veins. Yohimbine (alpha(2)-adrenoceptor receptor antagonist) and MK912 (alpha(2C)-adrenoceptor receptor antagonist), but not alpha(2A)- or alpha(2B)-adrenoceptor antagonists, produced rightward shifts in norepinephrine concentration-response curves in veins. Pharmacological studies revealed that alpha(1D)-adrenoceptors mediate venous constrictions. Norepinephrine responses in veins from alpha(2C)-adrenoceptor knock-out (KO) mice were not different from wild type veins. Yohimbine inhibited norepinephrine constrictions in alpha(2C)-adrenoceptor KO veins suggesting that there is upregulation of other alpha(2)-adrenoceptors in alpha(2C)-KO mice. These data indicate that alpha(1D)- and alpha(2C)-adrenoceptors interact in veins but not in arteries. This interaction enhances venous adrenergic reactivity. Mesenteric vein-specific alpha(2)-adrenoceptor linked Ca(2+) and perhaps other signaling pathways account for enhanced venous adrenergic reactivity.

• MeSH
• alfa-1-adrenergní receptory - agonisté farmakologie   MeSH
• alfa-1-adrenergní receptory metabolismus   fyziologie   MeSH
• alfa-2-adrenergní receptory - agonisté farmakologie   MeSH
• alfa-2-adrenergní receptory - antagonisté farmakologie   MeSH
• alfa-2-adrenergní receptory genetika   metabolismus   fyziologie   MeSH
• arteriae mesentericae účinky léků   fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• noradrenalin fyziologie   MeSH
• protein - isoformy antagonisté a inhibitory   MeSH
• sympatický nervový systém účinky léků   MeSH
• vápníková signalizace účinky léků   MeSH
• vazokonstrikce účinky léků   MeSH
• vena mesenterica účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• techniky in vitro MeSH

• MeSH
• agrese účinky léků   MeSH
• alfa-2-adrenergní receptory agonisté   antagonisté a inhibitory   MeSH
• behaviorální výzkum metody   MeSH
• dexmedetomidin analogy a deriváty   farmakologie   MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• ligandy MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• abstrakty MeSH

Studies on the neurotransmitter substrate of locomotion and place navigation occupy a central position in behavioral neuroscience. Active allothetic place avoidance (AAPA) is a task, in which animals are trained to avoid a room frame defined stable sector on a continuously rotating arena. The aim of the present study was to test the effect of the blockage of alpha1- and alpha2-adrenoceptors, using specific antagonists prazosin and idazoxan, on the locomotor activity and spatial behavior in the AAPA task. Both prazosin and idazoxan at the highest doses (4 and 6 mg/kg, respectively) were found to decrease the locomotor activity in the AAPA and they also impaired navigational performance. The results suggest that antagonizing alpha-adrenoceptors with systemically administered drugs affects locomotor activity together with avoidance behavior and does not cause a purely cognitive deficit in the AAPA task.

• MeSH
• alfa blokátory farmakologie   MeSH
• alfa-1-adrenergní receptory - antagonisté MeSH
• alfa-1-adrenergní receptory metabolismus   MeSH
• alfa-2-adrenergní receptory - antagonisté MeSH
• alfa-2-adrenergní receptory metabolismus   MeSH
• alfa-adrenergní receptory metabolismus   MeSH
• financování organizované MeSH
• idazoxan farmakologie   MeSH
• krysa rodu rattus MeSH
• mozek metabolismus   účinky léků   MeSH
• pohybová aktivita fyziologie   účinky léků   MeSH
• poruchy paměti chemicky indukované   patofyziologie   MeSH
• potkani Long-Evans MeSH
• prazosin farmakologie   MeSH
• učení vyhýbat se fyziologie   účinky léků   MeSH
• vnímání prostoru fyziologie   účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

S cílem objasnit, zda je hypotenzní a inhibiční působení na baroreflex vyvolané rilmenidinem zprostředkováno přímo imidazolinovými receptory v rostrální ventrolaterální medulle (RVLM), byla provedena preklinická studie s králíky. Po jednorázovém nitrožilním podání rilmenidinu došlo k výraznému poklesu krevního tlaku a ke snížení renální aktivity sympatiku, přičemž baroreflex se snížil o 33 %. Idazoxan (antagonista imidazolinových a a2-receptorů) aplikovaný do RVLM tento účinek zcela zrušil. Podobný účinek měl i čistý antagonista a2-receptorů – látka 2-MI –, což nasvědčuje skutečnosti, že mechanismem účinku rilmenidinu není pouze ovlivnění imidazolinových receptorů, ale i adrenergních a2-receptorů.

• MeSH
• agonisté adrenergních alfa-receptorů farmakologie   terapeutické užití   MeSH
• alfa-2-adrenergní receptory účinky léků   MeSH
• antihypertenziva klasifikace   terapeutické užití   MeSH
• baroreflex účinky léků   MeSH
• experimenty na zvířatech MeSH
• idazoxan farmakologie   terapeutické užití   MeSH
• králíci MeSH
• oxazoly MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH

The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

• MeSH
• alfa-2-adrenergní receptory metabolismus   MeSH
• dietní tuky MeSH
• dospělí MeSH
• fentolamin farmakologie   MeSH
• financování organizované MeSH
• inzulin metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza MeSH
• mastné kyseliny metabolismus   MeSH
• mikrodialýza MeSH
• obezita MeSH
• potraviny MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

• MeSH
• alfa-2-adrenergní receptory agonisté   aplikace a dávkování   MeSH
• antidepresiva tricyklická aplikace a dávkování   farmakologie   MeSH
• bupropion aplikace a dávkování   farmakologie   MeSH
• hyperkinetická porucha etiologie   farmakoterapie   MeSH
• karbamazepin aplikace a dávkování   farmakologie   MeSH
• komorbidita MeSH
• lidé MeSH
• lithium aplikace a dávkování   MeSH
• přehledová literatura jako téma MeSH
• psychotropní léky aplikace a dávkování   farmakologie   MeSH
• stimulancia historická aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH

Dexmedetomidine is a highly specific alpha2-adrenoreceptor agonist, which is now clinically used to induce sedation in patients in the intensive care units. Behavioural effects of dexmedetomidine have been little studied so far. The drug was reported to reduce behaviour such as locomotion or measures of anxiety or aggression in animals. The aim of the present study was to ascertain whether dexmedetomidine inhibits behaviour uniformly or with respect to particular stimuli or situations. Therefore, behavioural effects of dexmedetomidine were studied in the social conflict test in male mice (after three weeks of individual housing), which provides a wide spectrum of behavioural activities in two types of animals (aggressive and sociable mice) as well as in the activity cage. Dexmedetomidine (5-40 microg/kg i.p.) decreased locomotion in the activity cage and this effect was fully antagonized by atipamezole, a selective alpha2-adrenereceptor antagonist. However, dexmedetomidine did not reduce locomotion during social conflict. The only significant effects during social conflict were a selective and dose-dependent antiaggressive effect in aggressive mice and a selective reduction of social investigation ('sociability') in sociable mice. Thus, dexmedetomidine appears to inhibit predominantly dominant behaviour evoked by biologically important stimuli. The ability of dexmedetomidine to reduce aggression might be utilized for treatment of aggressive states. Sedation caused by dexmedetomidine can be easily disrupted and thus the drug may have an advantage over benzodiazepines or neuroleptics, which are used in this indication.

• MeSH
• agonisté adrenergních alfa-receptorů aplikace a dávkování   farmakologie   MeSH
• agrese účinky léků   MeSH
• alfa blokátory aplikace a dávkování   farmakologie   MeSH
• alfa-2-adrenergní receptory účinky léků   MeSH
• analýza rozptylu MeSH
• chování zvířat účinky léků   MeSH
• dexmedetomidin aplikace a dávkování   farmakologie   MeSH
• financování organizované MeSH
• imidazoly aplikace a dávkování   farmakologie   MeSH
• konflikt (psychologie) MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• sociální chování MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH