Morphine Protects Peroxynitrite-induced Cell Death in Primary Rat Neonatal Astrocytes / 대한마취과학회지

BACKGROUND: Astrocytes, representing a major non-neuronal cell population in the central nervous system (CNS), contain opioid receptors and are actively involved in several brain functions. This study is designed to evaluate the effects by which morphine contributes to cytotoxicity of nitric oxide (NO) species including NO and peroxynitrite (ONOO(-)) in primary astrocytes isolated from the cerebral cortexes of 1 - 2 day Sprague-Dawley rats. METHODS: The cultured cells were pretreated with morphine and exposed to 3-morpholinosydnonimine (SIN-1) which simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. The cell damage was assessed by using an MTT (methylthizol-2-yl-2, 5-diphenyl, tetrazolium bromide) assay. Morphological nuclear changes of the cells after exposure to SIN-1 for 24 hours was evaluated by using 4', 6-diamidino-2-phenylindole (DAPI) staining. RESULTS: Morphine significantly protected primary rat astrocytes in a dose-dependent manner from the death mediated by sodium nitroprusside (SNP), a donor of nitric oxide, and SIN-1. Moreover, it was found that naloxone antagonized the protective effect of morphine on SIN-1-induced cell death, revealed as apoptosis by the occurrence of morphological nuclear changes characteristic of apoptosis. Morphine also inhibited the nuclear condensation of SIN-1-treated cells, however the action of morphine was antagonized by pretreatment of naloxone. The protective role of morphine on SIN-1-induced cytotoxicity was inhibited by DL-Buthionine-[S, R]-sulfoximine (BSO). Furthermore, the effects of morphine on SIN-1-induced cytotoxicity were blocked by pretreatment of Gi protein inhibitor, pertussis toxin, and phosphoinositide 3-kinase (PI3 kinase) inhibitors, Wortmannin and LY294002. CONCLUSIONS: These results suggest that morphine may protect primary rat astrocytes from NO species via the signaling cascades involving G-protein and PI3-kinase, and possibly regulates the anti-oxidant, glutathione (GSH).

Influence of Respiratory and Metabolic Acid-Base Changes on the Effect of Nondepolarizing Muscle Relaxants in the Rat Phrenic-hemidiaphragm / 대한마취과학회지

The effects and interactions of metabolic and respiratory acid-base changes on electrically-evoked twitch response, train-of-four and tetanic stimulation with pipecuronium (Pip), vecuronium (Vec) and atracurium (Tra) were studied in the isolated rat hemi-diaphragm preparation. pip (3X10(-7) - 4X10(-6) M), Vec (3X10(-6) - 15X10(-6) M) and Tra (10(-6) - 3X10(-5) M) decreased the electrically-evoked (phrenic nerve stimulation, 0.1 Hz, 0.2 ms, 10 V) twitch response in a dose related fashion and Pip was more potent than Vec and Tra. In the alkali state (pH 7.6 or high HCO3 ), the decrements of twitch response, train-of-four and tetanus ratio induced by Pip (1.5uM) were potentiated, but the effects of Vec or Tra were markedly intensified by acid midium (pH 7.2 or low HCO3 ). And also, decreasing pH by increasing PCO2 or by decreasing HCO3 intensified the effects of Vec and Tra, whereas it reversed by Pip. Conversely, increasing pH by decreasing PCO2 or by increasing HCO3 antagonized the effects of Vec and Tra, whereas it potentiated the Pip effect. On the basis of these finding, the result of the present study suggest that neither PCO2 nor HCO3 has a specific action, but that changes in pH may be responsible for the results. In addition, the differences of the above results by each drugs may not be due to the number of quaternary ammonium of the agents. And also, indicate that the effective site of the influence of the acid-base change upon the neuromuscular blocking effects might be prejunctional nerve terminal.