Endojen nitrik oksit sentaz inhibitörü asimetrik dimetilargininin morfin tolerans ve bağımlılığındaki modülatör rolü
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Dosyalar
Tarih
2010
Yazarlar
Dergi Başlığı
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Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Asimetrik dimetilargininin artmış plazma düzeyleri birçok kardiyovasküler ve metabolik hastalıkla ilişkilidir. Bu çalışmada, endojen nitrik oksit sentaz inhibitörü asimetrik dimetilargininin, opioid bağımlılığı ve tolerans gelişiminde önemli katkısı olduğu hipotezini, farelerde morfine tolerans ve bağımlılık gelişirken plazma asimetrik dimetilarginin seviyelerinin ölçümü yoluyla araştırdık. Morfine tolerans ve bağımlılık, günde iki kez 10 mg/kg subkutan morfin injeksiyonuyla oluşturuldu. Fareler, 3, 6, 9 ve 10 gün beslenen gruplara ayrıldı. Tail flick testinde morfinin antinosiseptif etkisinin kaybı, tolerans gelişiminin derecesini belirlemek için kullanıldı. Fiziksel bağımlılık 5 mg/kg nalokson verilmesini takiben meydana gelen çekilme sendromu bulguları olan sıçrama ve ön pençe tremorlarının 20 dakika süresince sayılmasıyla belirlendi. Her beslenme periyodunun sonunda hayvanlara anestezi verilerek kalplerinden kan örnekleri alındı. Morfin tolerans ve bağımlılığı gelişen farelerde, asimetrik dimetilarginin, simetrik dimetilarginin, L-arginin ve L-homoarginin düzeyleri süre uyumlu kontrol gruplarına göre farklı değildi. Benzer olarak, tolerans ve bağımlılığın değişik aşamalarında olan fare gruplarındaki plazma asimetrik dimetilarginin ve diğer molekül konsantrasyonlarında da bir farklılık görülmedi. Sonuçlarımız morfin tolerans ve bağımlılığının gelişimi süresince endojen asimetrik dimetilarginin, simetrik dimetilarginin, L-arginin ve L-homoarginin düzeylerinin, hipotezimizle uyumsuz olarak değişmediğini göstermektedir. Anahtar sözcükler: Morfin, tolerans, bağımlılık, asimetrik dimetil arginin, nitrik oksit.
Abstract
Elevated plasma asymmetric dimethylarginine levels have been implicated in many cardiovascular and metabolic disorders. In the current work, we investigated the hypothesis that endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine is an important contributor to opioid tolerance and dependence, by determining plasma asymmetric dimethylarginine levels during the development of tolerance and dependence to morphine in mice. Tolerance to and dependence on morphine were induced by repeated injections of morphine (10 mg/kg, s.c.) twice daily to mice, divided into groups of 3, 6, 9 and 10 day feeding duration. The loss of antinociceptive effect of morphine in the tail flick test was used for evaluating the degree of tolerance. Physical dependence was assessed following the administration of a 5 mg/kg dose of naloxone, by counting the occurrence of withdrawal jumps and forepaw tremors for 20 min. At the end of each period, animals were anesthetized and blood samples were collected from the heart. The plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine and L-homoarginine in morphine tolerant and dependent mice were not different from duration-matched control mice. Similarly, no difference was observed in plasma asymmetric dimethylarginine and the other molecules concentrations between groups of mice with different stages of development of tolerance and dependence. Our results suggest that endogenous asymmetric dimethylarginine, symmetric dimethylarginine, homoarginine and L-arginin levels remain unchanged during the development of morphine tolerance and dependence, and are not associated with these phenomena. Keywords: morphine, tolerance, dependence, asymmetric dimethylarginine, nitric oxide.
Abstract
Elevated plasma asymmetric dimethylarginine levels have been implicated in many cardiovascular and metabolic disorders. In the current work, we investigated the hypothesis that endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine is an important contributor to opioid tolerance and dependence, by determining plasma asymmetric dimethylarginine levels during the development of tolerance and dependence to morphine in mice. Tolerance to and dependence on morphine were induced by repeated injections of morphine (10 mg/kg, s.c.) twice daily to mice, divided into groups of 3, 6, 9 and 10 day feeding duration. The loss of antinociceptive effect of morphine in the tail flick test was used for evaluating the degree of tolerance. Physical dependence was assessed following the administration of a 5 mg/kg dose of naloxone, by counting the occurrence of withdrawal jumps and forepaw tremors for 20 min. At the end of each period, animals were anesthetized and blood samples were collected from the heart. The plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine and L-homoarginine in morphine tolerant and dependent mice were not different from duration-matched control mice. Similarly, no difference was observed in plasma asymmetric dimethylarginine and the other molecules concentrations between groups of mice with different stages of development of tolerance and dependence. Our results suggest that endogenous asymmetric dimethylarginine, symmetric dimethylarginine, homoarginine and L-arginin levels remain unchanged during the development of morphine tolerance and dependence, and are not associated with these phenomena. Keywords: morphine, tolerance, dependence, asymmetric dimethylarginine, nitric oxide.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
Eczacılık, Farmakoloji, Pharmacy, Pharmacology, Morfin, Tolerans, Bağımlılık, Asimetrik Dimetil Arginin, Asymmetric Dimethylarginine
