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A study of adenosine receptors and their signaling in the rat myocardium
Eichlerová, Lenka ; Novotný, Jiří (advisor) ; Nováková, Olga (referee)
Adenosine plays a critical role in the heart signalling while affecting heart rate, contractility or coronary flow. Nowadays, four adenosine receptor subtypes are distinguished which are present in most of tissues and cells: A1, A2A, A2B and A3. All these receptors belong to the family of G protein-coupled receptors. Upon activation, their main target is an enzyme adenylyl cyclase which produces an important second messenger cAMP. The main goal of this thesis was characterization of adenosine receptors in the rat myocardium, assessment of their distribution, binding properties and signalling. We examined a possible disparity in receptors distribution between the left and right ventricles using SDS-PAGE electrophoresis and Western blotting. The same methods have been used in studies of adenosine receptor distribution in lipid rafts. Samples of lipid rafts and soluble fraction were prepared using a nonionic detergent Triton X-100. We did not find any evidence of different distribution between the left and right ventricles and our results did not confirm compartmentation of the receptors either. For determination of binding properties of the receptors we used radioligand binding assays with the A1 selective radioligand [H3 ]DPCPX. We did not observe any significant difference between the receptor...
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Molecular physiology of adenosine receptors
Eichlerová, Lenka ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
Adenosine mediates its physiological signaling functions through the interaction with four receptor subtypes. The adenosine receptors belong to the superfamily of G protein-coupled receptors and are named A1, A2A, A2B and A3 receptors. Since they are widespread throughout the body, they are involved in many physiological processes and dysfunction of the adenosine system may have serious pathological consequences. Activity of adenosine receptors is inhibited by methylxanthines. Caffeine is a typical non-selective antagonist of the receptors, which is known to affect the sleep cycle. A great progress occurred in understanding the structure of adenosine receptors after the crystallographic model was solved for A2A receptor in complex with the antagonist ZM241385, which is referred to as super-caffeine. Understanding the receptor structure as well as the molecular mechanisms underlying the regulation of their function and interactions represent a starting point to the development of new drugs, which are going to be highly efficient and selective for each adenosine receptor subtype.
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A study of adenosine receptors and their signaling in the rat myocardium
Eichlerová, Lenka ; Novotný, Jiří (advisor) ; Nováková, Olga (referee)
Adenosine plays a critical role in the heart signalling while affecting heart rate, contractility or coronary flow. Nowadays, four adenosine receptor subtypes are distinguished which are present in most of tissues and cells: A1, A2A, A2B and A3. All these receptors belong to the family of G protein-coupled receptors. Upon activation, their main target is an enzyme adenylyl cyclase which produces an important second messenger cAMP. The main goal of this thesis was characterization of adenosine receptors in the rat myocardium, assessment of their distribution, binding properties and signalling. We examined a possible disparity in receptors distribution between the left and right ventricles using SDS-PAGE electrophoresis and Western blotting. The same methods have been used in studies of adenosine receptor distribution in lipid rafts. Samples of lipid rafts and soluble fraction were prepared using a nonionic detergent Triton X-100. We did not find any evidence of different distribution between the left and right ventricles and our results did not confirm compartmentation of the receptors either. For determination of binding properties of the receptors we used radioligand binding assays with the A1 selective radioligand [H3 ]DPCPX. We did not observe any significant difference between the receptor...
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Molecular physiology of adenosine receptors
Eichlerová, Lenka ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
Adenosine mediates its physiological signaling functions through the interaction with four receptor subtypes. The adenosine receptors belong to the superfamily of G protein-coupled receptors and are named A1, A2A, A2B and A3 receptors. Since they are widespread throughout the body, they are involved in many physiological processes and dysfunction of the adenosine system may have serious pathological consequences. Activity of adenosine receptors is inhibited by methylxanthines. Caffeine is a typical non-selective antagonist of the receptors, which is known to affect the sleep cycle. A great progress occurred in understanding the structure of adenosine receptors after the crystallographic model was solved for A2A receptor in complex with the antagonist ZM241385, which is referred to as super-caffeine. Understanding the receptor structure as well as the molecular mechanisms underlying the regulation of their function and interactions represent a starting point to the development of new drugs, which are going to be highly efficient and selective for each adenosine receptor subtype.
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