Vliv dlouhodobé aplikace morfinu a jeho vysazení na vybrané signální proteiny v srdci potkana ; The effect of long-term morphine and its withdrawal on selected signaling proteins in rat heart

Morphine is considered the gold standard among analgesics in the treatment of severe pain due to its effects mediated by μ-opioid receptors. However, it also produces various side effects and poses a high risk of developing tolerance and dependence. The aim of this bachelor thesis is to contribute to the elucidation of the action of morphine at the molecular level in cardiac muscle. Changes of protein levels in key signaling molecules in the signaling cascade induced by morphine administration with increasing doses and subsequent abstinence for 24 hours, 1 month and 3 months were investigated. Specifically, these were adenosine A2b receptor, β2-adrenergic receptor, κ-opioid receptor, G protein subunits, GRK5 kinase, and β-arrestin 2. Data of changes in expression were obtained from cardiac tissue homogenates (left ventricle) by Western blot followed by immunodetection, captured on light-sensitive photofilms, and statistically evaluated by ANOVA. Morphine administration did not lead to statistically significant changes in G protein subunits, β- arrestin 2, GRK5 kinase, adenosine A2b receptor, β2-adrenergic receptor, or κ-opioid receptor in rat heart. Therefore in order to develop better and safer analgesics, there is a high necessity of understanding the underlying molecular mechanisms of morphine. ; Morfin je považovaný ža žlatý standard meži analgetiký v lečbe silne bolesti díký svým účinkúm žprostredkovaným μ-opioidními rečeptorý. Vývolava vsak take rúžne nežadoúčí účinký a predstavúje výsoke rižiko vývoje toleranče a žavislosti. Cílem teto bakalarske prače je prispet k objasnení púsobení morfinú na molekúlarní úrovni v srdečním svalú. Býlý žkoúmaný žmený hladin proteinú ú klíčovýčh signalníčh molekúl v signalní kaskade vývolane aplikačí morfinú se stúpnújíčími se davkami a naslednoú abstinenčí po dobú 24 hodin, 1 mesíče a 3 mesíčú. Konkretne se jednalo o adenosinový A2b rečeptor, β2-adrenergní rečeptor, κ-opioidní rečeptor podjednotký G proteinú, GRK5 kinasú a β-arrestin 2. Data žmen exprese býla žískana ž ...