BACKGROUND: Chronic renal failure is frequently associated with a high risk of sudden cardiac death due to dysfunction of the autonomic nervous system. The pathogenic mechanisms underlying the parasympathetic cardiac dysautonomia are not fully elucidated yet. METHODS: Chronic renal failure was induced in rats by 5/6 nephrectomy. Blood pressure, resting heart rate and plasma levels of creatinine, urea and asymmetric dimethylarginine (ADMA) were measured. To characterize the parasympathetic innervation of the heart, chronotropic responses to atropine, metipranolol and to vagal stimulation in the absence or presence of ADMA were investigated in vivo. In vitro, chronotropic and inotropic effects of carbachol and ADMA and mRNA expression of muscarinic M2 receptors, high affinity choline transporter (CHT1), vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) were assessed in the isolated cardiac tissues. RESULTS: In 5/6 nephrectomy rats, the resting heart rate was significantly higher and the parasympathetic tone, measured as the effect of atropine after administration of metipranolol was significantly lower than in control animals. Plasma ADMA levels were significantly elevated in the uraemic rats and significantly inversely correlated with the effect of atropine on the heart rate. No differences were revealed in the plasma norepinephrine concentrations, negative chronotropic responses to stimulation of the vagus nerves, chronotropic and inotropic responses to carbachol and the relative expression of M2 receptors, CHT1, VAChT and ChAT. CONCLUSION: The data suggest that cardioacceleration in chronic renal failure is caused by a diminished cardiac parasympathetic tone in the presence of a functionally intact intrinsic cardiac cholinergic signalling system.

• MeSH
• atropin farmakologie   MeSH
• beta blokátory farmakologie   MeSH
• cholin-O-acetyltransferasa genetika   metabolismus   MeSH
• karbachol farmakologie   MeSH
• kardiotonika farmakologie   MeSH
• krysa rodu rattus MeSH
• ledviny chirurgie   metabolismus   účinky léků   MeSH
• messenger RNA genetika   metabolismus   MeSH
• metipranolol farmakologie   MeSH
• nefrektomie MeSH
• nervus vagus fyziologie   účinky léků   MeSH
• noradrenalin metabolismus   MeSH
• parasympatický nervový systém fyziologie   účinky léků   MeSH
• parasympatolytika farmakologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Wistar MeSH
• proteiny nervové tkáně genetika   metabolismus   MeSH
• proteiny přenášející neurotransmitery přes plazmatickou membránu genetika   metabolismus   MeSH
• srdce inervace   MeSH
• srdeční frekvence fyziologie   MeSH
• vezikulární transportní proteiny acetylcholinu genetika   metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

Various sources of protein data, such as knowledgebases and scientific literature, are currently available, as are numerous tools for their analysis. The matter becomes one of choosing the tools that are most appropriate for the specific task and for the specific proteins. A combination of standard and alternative tools may lead to biologically significant results. Here, a computational classification of proteins is made using standard multiple sequence alignment in combination with an alternative method for analysis of hydropathy distribution in proteins. Both of these methods are applied to the Na+/Cl--dependent neurotransmitter symporters (NSSs), resulting in two alternative classifications. The classifications are validated and interpreted biologically by literature and knowledgebase annotation mining, producing a consensus classification. The classification leads to the identification and functional characterization of three families of largely structurally and functionally uncharacterized orphan NSSs. The literature and knowledgebase annotations are mined to functionally characterize the NSSs in these families. The presented work also demonstrates that, in specific cases, the analysis of the hydropathy distribution in proteins is capable of revealing functional properties of proteins.

• MeSH
• databáze proteinů MeSH
• financování organizované MeSH
• hydrofobní a hydrofilní interakce MeSH
• mapování interakce mezi proteiny klasifikace   MeSH
• proteiny přenášející neurotransmitery přes plazmatickou membránu klasifikace   metabolismus   MeSH
• sekvenční analýza proteinů metody   MeSH
• sekvenční seřazení MeSH
• výpočetní biologie metody   MeSH
• znalostní báze MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH
• validační studie MeSH