The slow delayed rectifier potassium current (IKs) significantly contributes to cardiac repolarization under specific conditions, particularly at stimulation by the protein kinase A (PKA) during increased sympathetic tone. Impaired PKA-mediated stimulation of IKs channels may considerably aggravate dysfunction of the channels induced by mutations in the KCNQ1 gene that encodes the structure of the α-subunit of IKs channels. These mutations are associated with several subtypes of inherited arrhythmias, mainly long QT syndrome type 1, less commonly short QT syndrome type 2, and atrial fibrillation. The impaired PKA reactivity of IKs channels may significantly increase the risk of arrhythmia in these patients. Unfortunately, only approximately 2.7% of the KCNQ1 variants identified as putatively clinically significant have been studied with respect to this problem. This review summarizes the current knowledge in the field to stress the importance of the PKA-mediated regulation of IKs channels, and to appeal for further analysis of this regulation in KCNQ1 mutations associated with inherited arrhythmogenic syndromes. On the basis of the facts summarized in our review, we suggest several new regions of the α-subunit of the IKs channels as potential contributors to PKA stimulation, namely the S4 and S5 segments, and the S2-S3 and S4-S5 linkers. Deeper knowledge of mechanisms of the impaired PKA response in mutated IKs channels may help to better understand this regulation, and may improve risk stratification and management of patients suffering from related pathologies.

• MeSH
• beta-adrenergní receptory fyziologie   MeSH
• draslíkový kanál KCNQ1 genetika   MeSH
• fosforylace MeSH
• lidé MeSH
• mutace MeSH
• pozdní usměrňovače draslíkových kanálů fyziologie   MeSH
• převodní systém srdeční fyziologie   MeSH
• proteinkinasy závislé na cyklickém AMP fyziologie   MeSH
• syndrom dlouhého QT genetika   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• beta-adrenergní receptory MeSH
• draslíkový kanál KCNQ1 MeSH
• pozdní usměrňovače draslíkových kanálů MeSH
• proteinkinasy závislé na cyklickém AMP MeSH

The regulation of heart function is one of the essentials for the survival of organism. Therefore, the effective mechanisms of regulation can minimize the energy requirements and improve the ability to react to different needs on time and appropriately. Two receptor types, beta-adrenoceptors and muscarinic receptors, with almost antagonistic function, are "basic regulators" of the heart parameters. It is relevant to mention that beside the main adrenoceptors and muscarinic receptors subtypes (beta(1)- and M(2)-subtype), other minor subtypes that regulate heart function, i.e. beta-, beta-adrenoceptors, alpha(1)-adrenoceptors and minor subtypes of muscarinic receptors (M(1), M(3) and M(5)) are present in the heart. In this regard is intriguing that just two catecholamines (adrenaline, noradrenaline) have many "targets"--receptors that differ so much in the functional consequences of their activation: while beta(1)- and beta(2)-adrenoceptors cause cardiostimulation, beta(3)-adrenoceptors are responsible for cardioinhibition and alpha(1)-adrenoceptors contribute to enhanced inotropy. Similarly, some data show that other muscarinic receptors than M(2) muscarinic subtype, are expressed in the heart and these minor subtype(s) can contribute to the heart regulation in similar way as beta(3)-adrenoceptors to the catecholamine action. Taken together, regulation of heart function through different receptor subtypes and using homologous and heterologous regulation can represent an effective tool for coping with permanently changing environmental conditions.

• MeSH
• beta-adrenergní receptory fyziologie   MeSH
• biologické modely MeSH
• lidé MeSH
• receptory muskarinové fyziologie   MeSH
• receptory spřažené s G-proteiny fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• srdce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• beta-adrenergní receptory MeSH
• receptory muskarinové MeSH
• receptory spřažené s G-proteiny MeSH

The development of heart rate and of muscarinic and beta-adrenergic receptors in chick heart ventricles in the last third of in ovo ontogenesis has been studied. The development of these two types of autonomic receptors does not proceed in parallel. While muscarinic receptors are stable between days 13 and 17, beta-adrenergic receptors significantly decrease in this period. Muscarinic receptors increase their number from the 17th day, and the highest density can be seen after hatching. beta-adrenergic receptors, on the contrary, do not change their density between days 17 and 19, but similarly to muscarinic receptors they increase after hatching (the density after hatching is approximately the same as on the day 13 of embryonic development). We have shown previously that stimulation of one receptor type in the system of autonomic receptors in the heart changes not only the appropriate type of receptor but also the density of the other one. We therefore wondered the information about this in the organism in development. Here we show that when we have infused the eggs in developmental period mentioned above there was no cross-regulation and that muscarinic receptors do not down-regulate. Up-regulation of muscarinic receptors was maintained when the eggs were infused by carbachol from the 13th to 14th day of in ovo development. This muscarinic receptor up-regulation was accompanied with paradoxical increase in heart rate. These events are not proteinkinase (PKC) dependent, as bisindolylmaleimide (PKC inhibitor) do not prevent these changes.

• MeSH
• beta-adrenergní receptory účinky léků   fyziologie   MeSH
• cholinergní agonisté aplikace a dávkování   farmakologie   MeSH
• indoly aplikace a dávkování   farmakologie   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• karbachol aplikace a dávkování   farmakologie   MeSH
• kuřecí embryo MeSH
• maleimidy aplikace a dávkování   farmakologie   MeSH
• receptory muskarinové účinky léků   fyziologie   MeSH
• srdce embryologie   inervace   MeSH
• srdeční frekvence účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-adrenergní receptory MeSH
• bisindolylmaleimide MeSH Prohlížeč
• cholinergní agonisté MeSH
• indoly MeSH
• inhibitory proteinkinas MeSH
• karbachol MeSH
• maleimidy MeSH
• receptory muskarinové MeSH

Glucocorticoids affect the expression and density of neurotransmitter receptors in many tissues but data concerning the heart are contradictory and incomplete. We injected rats with hydrocortisone for 1-12 days and measured the densities of cardiac muscarinic receptors, alpha(1)-, beta(1)- and beta(2)-adrenoceptors and propranolol-resistant binding sites (formerly assumed to be the putative beta(4)-adrenoceptor). Some aspects of intracellular signalling were also evaluated: we measured adenylyl cyclase activity (basal, isoprenaline- and forskolin-stimulated and carbachol-inhibited), the coupling between muscarinic receptors and G proteins and basal and isoprenaline-stimulated heart rate. The density of cardiac muscarinic receptors increased (in both the atria and the ventricles). The density of beta(1)-adrenoceptors increased in the atria and was little changed in the ventricles. The density of beta(2)-adrenoceptors increased in both the atria and the ventricles. The number of alpha(1)-adrenoceptors decreased initially, followed by a transient increase in the atria and did not change in the ventricles. The density of propranolol-resistant binding sites first increased and then diminished in the atria and did not change in the ventricles. Although there were noticeable changes in receptor densities, the stimulatory and inhibitory effects on adenylyl cyclase, basal and isoprenaline-stimulated heart rate and the coupling between muscarinic receptors and G proteins were not significantly altered. This may indicate that changes in receptor densities might be one of the mechanisms maintaining stable functional output.

• MeSH
• adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• alfa-1-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• beta blokátory farmakologie   MeSH
• beta-1-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• beta-2-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• beta-adrenergní receptory účinky léků   metabolismus   fyziologie   MeSH
• glukokortikoidy aplikace a dávkování   farmakologie   MeSH
• hydrokortison aplikace a dávkování   farmakologie   MeSH
• injekce subkutánní MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• potkani Wistar MeSH
• propanolaminy farmakologie   MeSH
• propranolol farmakologie   MeSH
• radioligandová zkouška MeSH
• receptory muskarinové účinky léků   metabolismus   fyziologie   MeSH
• signální transdukce účinky léků   MeSH
• srdeční komory účinky léků   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adrenergic beta-4 receptor MeSH Prohlížeč
• adrenergní receptory MeSH
• alfa-1-adrenergní receptory MeSH
• beta blokátory MeSH
• beta-1-adrenergní receptory MeSH
• beta-2-adrenergní receptory MeSH
• beta-adrenergní receptory MeSH
• CGP 12177 MeSH Prohlížeč
• glukokortikoidy MeSH
• hydrokortison MeSH
• propanolaminy MeSH
• propranolol MeSH
• receptory muskarinové MeSH

OBJECTIVE: The aim of this study was to assess, by longitudinal follow-up, the influence of aerobic training on the in vivo lipolytic activity of adipose tissue in obese male subjects. SUBJECTS: Eleven obese non-diabetic males, aged 41.5+/-5.77 (range 27-49 y) with body mass index (BMI) 36.5+/-4.5 kg/m2 (range 29.4-47.1 kg/m2) participated in the study. DESIGN: Subjects took part in a 12-week aerobic training program. Before and after training, microdialysis of abdominal subcutaneous adipose tissue (SCAT) was carried out, using perfusion with graded doses of the beta-adrenergic agonist isoprenaline and a single dose of the phosphodiesterase inhibitor theophylline. In addition, the response of plasma glycerol and free fatty acids (FFAs) to intravenous infusion of graded doses of isoprenaline was tested. RESULTS: The training did not induce significant weight loss and promoted an increase in maximum aerobic capacity (P<0.05). The increase of extracellular glycerol in SCAT in response to isoprenaline perfusion was enhanced after the training (P<0.05), while no change in the response of interstitial glycerol to theophylline action was observed. The training did not elicit a change in the isoprenaline-induced changes of blood flow in adipose tissue. The increases of plasma FFAs and glycerol in response to intravenous isoprenaline infusion, were significantly enhanced after training. CONCLUSION: The present study shows that aerobic training induced an increase in the response of plasma and subcutaneous adipose tissue concentration of glycerol to beta-adrenergic stimulation. The effect of an agent acting at the post-receptor level (theophylline) in SCAT was not modified by training.

• MeSH
• agonisté adrenergních beta-receptorů aplikace a dávkování   MeSH
• beta-adrenergní receptory fyziologie   MeSH
• cvičení * MeSH
• dospělí MeSH
• fyzická vytrvalost * MeSH
• glukózový toleranční test MeSH
• glycerol krev   MeSH
• inhibitory fosfodiesteras aplikace a dávkování   MeSH
• isoprenalin aplikace a dávkování   MeSH
• kyseliny mastné neesterifikované krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• lipolýza * MeSH
• mikrodialýza MeSH
• obezita metabolismus   terapie   MeSH
• theofylin aplikace a dávkování   MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté adrenergních beta-receptorů MeSH
• beta-adrenergní receptory MeSH
• glycerol MeSH
• inhibitory fosfodiesteras MeSH
• isoprenalin MeSH
• kyseliny mastné neesterifikované MeSH
• lipidy MeSH
• theofylin MeSH

Muscarinic and beta-adrenergic receptors belongs to the family of G protein coupled receptors. Their activation brings about nearly antagonistic effects in most tissues. We demonstrate on the model of myocardial cells, that their regulation is mutually interconnected and that the cross-regulation could represent new level of homeostasis maintenance.

• MeSH
• beta-adrenergní receptory fyziologie   MeSH
• homeostáza MeSH
• lidé MeSH
• myokard metabolismus   MeSH
• receptory muskarinové fyziologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• beta-adrenergní receptory MeSH
• receptory muskarinové MeSH

• MeSH
• adrenalin fyziologie   MeSH
• aklimatizace MeSH
• beta-adrenergní receptory fyziologie   MeSH
• energetický metabolismus účinky léků   MeSH
• isoprenalin farmakologie   MeSH
• krevní tlak účinky léků   MeSH
• lidé MeSH
• nízká teplota MeSH
• noradrenalin fyziologie   MeSH
• srdeční frekvence účinky léků   MeSH
• termoregulace * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adrenalin MeSH
• beta-adrenergní receptory MeSH
• isoprenalin MeSH
• noradrenalin MeSH

We studied the effects of hydrogen peroxide, hypochlorous acid and ozone on muscarinic and beta-adrenergic receptor responses in guinea pig tracheal tissue. Pretreatment of the tracheal strips with hydrogen peroxide (up to 10 mM) did not affect the muscarinic or beta-adrenergic receptor responses after stimulation with methacholine or (-)-isoprenaline respectively. In contrast to hydrogen peroxide, hypochlorous acid (1 mM and 10 mM) decreased the maximal contraction and the pD2-value after stimulation with the muscarinic agonist methacholine. Comparable effects were observed after stimulation with the beta-adrenoceptor agonist (-)-isoprenaline but the beta-adrenoceptor response seemed to be more susceptible to hypochlorous acid treatment than the muscarinic response. In other words, hypochlorous acid changes the balance between muscarinic and beta-adrenergic receptor responses of guinea pig tracheal strips in favour of the muscarinic receptor responses. In vivo exposure of the guinea pigs to 3 ppm ozone for two hours resulted in a hyperreactivity (increase in maximal contraction) after stimulation of the muscarinic receptor with methacholine. No effects were observed in the pD2-value. The beta-adrenergic receptor response was also affected after ozone exposure. No effects were seen in the maximal (-)-isoprenaline induced relaxation but there was an increase (hypersensitivity) in the pD2-value. Our data suggest that oxidative stress modulates receptor responses. Moreover, the type of oxidant seems to differentially affect various receptor responses. This may be of importance to further understand the influence of an oxidative effect (either directly via ozone or through inflammation) in lung tissue.

• MeSH
• beta-adrenergní receptory fyziologie   MeSH
• bronchiální hyperreaktivita patofyziologie   MeSH
• bronchokonstrikce fyziologie   MeSH
• kultivační techniky MeSH
• kyselina chlorná farmakologie   MeSH
• morčata MeSH
• oxidační stres fyziologie   MeSH
• ozon farmakologie   MeSH
• peroxid vodíku farmakologie   MeSH
• receptory muskarinové fyziologie   MeSH
• trachea metabolismus   MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-adrenergní receptory MeSH
• kyselina chlorná MeSH
• ozon MeSH
• peroxid vodíku MeSH
• receptory muskarinové MeSH

The beta-adrenergic stimulation of adenylyl cyclase is mediated through the stimulatory G-protein (Gs). In this study, three synthetic peptides corresponding to different regions (amino acids 3-14, 72-86 and 325-337) of the alpha subunit of Gs (Gs-alpha) have been employed in competition assays in order to examine more closely the molecular basis of receptor-Gs-alpha interaction. The direct coupling between Gs and adenylyl cyclase was not influenced by any of these peptides and only the peptide representing residues 325-337 of Gs-alpha specifically inhibited beta-adrenergic receptor-mediated activation of Gs. Essentially the same results were obtained when testing beta-1- and beta-2-adrenergic receptors, which supports the notion that both these pharmacologically distinct receptor subtypes exploit at least one identical coupling domain within Gs-alpha for its activation.

• MeSH
• adenylátcyklasy metabolismus   MeSH
• beta-adrenergní receptory účinky léků   fyziologie   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• molekulární sekvence - údaje MeSH
• myokard metabolismus   MeSH
• novorozená zvířata MeSH
• peptidové fragmenty chemická syntéza   farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• proteiny vázající GTP chemie   fyziologie   MeSH
• sekvence aminokyselin MeSH
• signální transdukce * účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenylátcyklasy MeSH
• beta-adrenergní receptory MeSH
• peptidové fragmenty MeSH
• proteiny vázající GTP MeSH

Nonobese, hereditary hypertriglyceridemic (HTG) rats provide an interesting model of hypertriglyceridemia, glucose intolerance, and hypertension. In age-matched 15 HTG and 16 control Wistar rats fed on a high sucrose diet (70 cal%) for 6 weeks, we measured insulin sensitivity in vivo and some parameters of sympatoadrenal system. Using euglycemic clamps with administration of 2-deoxy[1-3H]glucose, we found whole body insulin resistance and decreased glucose metabolic index Rg' in soleus muscle, epitrochlearis muscle, diaphragm, and white adipose tissue in HTG rats. We found higher levels of plasma epinephrine and higher excretion of vanilmandelic and homovanilic acids in HTG rats. The binding of [3H]-dihydroalprenol to the heart membrane fraction was similar in both groups, but the dissociation constant Kd was increased by 75% in the heart of HTG rats.

• MeSH
• adrenalin krev   MeSH
• beta-adrenergní receptory fyziologie   MeSH
• dihydroalprenolol metabolismus   MeSH
• glukosa metabolismus   MeSH
• glykemický clamp MeSH
• hypertriglyceridemie genetika   patofyziologie   MeSH
• inzulin krev   MeSH
• inzulinová rezistence * MeSH
• krevní glukóza metabolismus   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• kyselina homovanilová moč   MeSH
• kyselina vanilmandlová moč   MeSH
• potkani Wistar MeSH
• svaly metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adrenalin MeSH
• beta-adrenergní receptory MeSH
• dihydroalprenolol MeSH
• glukosa MeSH
• inzulin MeSH
• krevní glukóza MeSH
• kyselina homovanilová MeSH
• kyselina vanilmandlová MeSH