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The effect of morphine on the distribution of signaling molecules of the opioid system in lipid rafts prepared from rat heart
Ladislav, Marek ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
Morphine is an opioid agonist, which can exert cardioprotective effects under certain conditions. Lipid rafts are considered important platforms for membrane organization of signaling proteins and, therefore, these structures could play a role in the effects of morphine, which acts through the opioid receptors. The aim of this thesis was to investigate the distribution of the main components of the opioid receptor and Gi/o-mediated signaling pathway in lipid rafts isolated from rat myocardium, which was affected by various doses of morphine. Because we used different isolation techniques with different solubilization agents (Triton X-100, CHAPS, cholate and sodium carbonate) for preparation of lipid rafts, it was of interest to characterize more closely these preparations. Another aim of this study was to investigate how different methods of isolating these structures affect activity of the key target enzyme of the opioid signaling pathway, i.e. adenylyl cyclase. The presence of signaling molecules of the Gi/o/AC pathway of the opioid system in membrane rafts was confirmed and the distribution of selected proteins was dependent on the type of extractant. We also observed the effect of morphine on the localization of proteins in lipid rafts. Different extractants provided different degree of...
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Effect of morphine on the resistance of the heart to ischemia
Mošovská, Linda ; Neckář, Jan (advisor) ; Žurmanová, Jitka (referee)
2. Abstract Opioids are considered as dangerous and addictive substances, mainly due to synthetic opioids such as heroin. It was discovered, that these substances can play an important role in myocardial ischemia because they can limit the damage of the heart tissue that occurs during a heart attack. Since that heart attack is the most common cardiovascular disease, the protective effect is significant. Cardioprotective effect is mainly mediated through δ opioid receptors, but the few studies have shown cardioprotective effect mediated through κ opioid receptors. The protective effect occurs by activation of opioid receptors by their agonists (eg. morphine or TAN-67), either before ischemia (opioid preconditioning) or before reperfusion (opioid postconditioning). The signaling pathway of cardioprotection include mitochondrial KATP channel, Gi/o proteins, protein kinase C, tyrosine kinases and reactive oxygen species.
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Effect of chronic morphine treatment of rats on myocardial signaling systems regulated by trimeric G-proteins
Škrabalová, Jitka ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
It has recently been discovered that the effect of morphine can significantly reduce the tissue damage that occurs during myocardial ischemia. The molecular mechanisms by which morphine acts on the heart are still little understood. The aim of this thesis was to monitor the effect of chronic 27-day and 10-day administration of low (1 mg/kg/day) and high (10 mg/kg/ day) doses of morphine on the expression of selected G-protein-coupled receptors (GPCR) and on the expression and activity of adenylyl cyclase (AC). Chronic (27 days) morphine treatment reduced the expression of к-opioids receptors, but 10-day morphine exposure did not influence the expression of these receptors. Assessment of β1- and β2-AR by immunoblot technique did not show any significant change in the expression, but the more accurate determination of β-AR expression using the saturation binding studies revealed that 27-day treatment with high doses of morphine appreciable increased the total number of these receptors. Administration of high doses of morphine led to marked up-regulation of adenylyl cyclase (AC) isoforms V/VI, and the amount of AC decreased proportionally with the time of discontinuation of morphine administration. Low doses of morphine up- regulated AC only during 27-day administration. Chronic morphine exposure did...
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The effect of morphine on expression and distribution of the alpha and beta subunits of trimeric G-proteins in the rat myocardium
Bartoňová, Iveta ; Novotný, Jiří (advisor) ; Roubalová, Lenka (referee)
Morphine is a clinically very important drug from the opioid group that is used for treatment of severe pain because of its strong analgetic effect. Opioid receptors mediating the morphine effect interact with the Gi/o class of trimeric G-proteins. Opioid receptors also occur in heart tissue and morphine can thus potentially exercise its effect on the function of this organ. The major aim of this project was to pursue consequences of long-term treatment with morphine on expression and distribution of selected heterotrimeric G-protein subunits in the rat heart. Potential cardioprotective effects of this drug have also been studied. Laboratory rats of the Wistar strain were treated with morphine (1 mg/kg/day or 10 mg/kg/day) for 10 or 28 days. The control group was treated with saline solution. Prolonged treatment with morphine did not cause any effects on Gs, Gi, Gz, Gq/11, G subunits, but the expression of Go rather decreased. The results of subsequent experiments showed that prolonged administration of high doses of morphine may reduce the area affected by infarction and reduced the frequency of ventricle arrhythmias depending on dose and duration of morphine administration. Key words: morphine, myocardium, opioid receptor, G-protein subunits, infarction.
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Potential role of opioids in neuroprotection
Gebauer, Martin ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
The opioids have been used by mankind for more than two millennia, but effect and mechanism of their action on the cells has been unveiling in the last few decades. The mechanism itself is often still unknown, but its effect is observed only. There are several groups of opioid receptors which are able to bind opioids. These groups are characterized by their differe nt affinity to opioids, in some cases by their different effects on cells and by their representation in the various areas in the CNS. Thus, the effects induces by these opioid are very different in many cases. This thesis summarizes the current knowledge about coronary heart disease and the potential of opioids for the prevention and their effect during ischemia, also summarizes the effects of morphine on the CNS. During ischemia δ-opioid receptors play a major role, because they inhibit or block the proapoptotic effects of ischemia on many levels. These receptors are also involved in inducing and maintaining the animal hibernation and protect animal's body against very harmful effects of hibernation, e.g lack of oxygen and nutrients. Morphine is opioid which has been used as anesthetic for longest time. It is well-known opioid and it has the most known derivates. This thesis also summarizes most significant effects of morphine on...
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Clinical importance and mechanisms of action of morphine and methadone
Slušná, Michaela ; Hejnová, Lucie (referee) ; Novotný, Jiří (advisor)
This bachelor thesis deals with gathering the information regarding the clinical importance of opioid drugs, particularly morphine and methadone, and their mechanism of action. Awareness of health professionals and the general public on opioid is inadequate. This evokes unnecessary anxiety of uninformed patients by the treatment of this kind of drugs. This thesis contains information that should know each worker in the health sector. It deals with pharmacodynamics, which is important for understanding the effects of drugs, both biochemical and physiological as well as pharmacokinetics, which describes how the body compensates for the delivered drug. Usage of morphine and methadone is currently irreplaceable. Morphine is a strong analgesic effective control of pain of different origin. Methadone is used for the substitutive treatment of people addicted to opioids. The side effects occurring during the treatment with opioids are acceptable with regard to severe pain, which is attenuated by opioids.
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The application of opioids in crews of medical rescue service
MATOUŠEK, Jan
The aim set by this bachelor thesis is to survey the application of opioids in the emergency crews. To meet this objective, I posed two research questions. Research question Nr. 1: Are patients informed about the application of opioids? Research question Nr. 2: Do paramedics find out the effects of opioids administered to patients? Patients are entitled by law to information about administering any medicaments, according to Health Care of the Population Act. The back check of effects of medicaments administered is important for the check-up of the efficiency of the dose administered as well as the danger of undesired effects. Opioid substances are derived from morphine. Morphine, which is found in the juice of opium poppy, has been used throughout history to produce euphoric effects and especially as an analgesic. The reason for using analgesics is pain, and for that reason I explain here what pain is, how it is classified, measured and especially how it is soothed. Opioids are substances used for soothing severe pains for which non-opioid analgesics are insufficient. However, using these substances may result in addiction, and therefore manipulation with them is strictly controlled by law. To achieve the objective I conducted quantitative research, and data were collected by a secondary data analysis, the method of questioning and interview technique. Drawing on the research results that were obtained by observing paramedics and from interviews with their patients, it appears that it is necessary to inform patients that they are being administered an opioid substance. There are exceptional states when patients are not able to perceive such information and their consent to administering the medicine can be supposed. It was observed that paramedics make a back proof of the effects of the medicaments administered, and it was also found out that there are paramedics who, in the event that the dose of medicament is inefficient, do nothing more.
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