İn vitro sıçan mesane kasılmaları üzerine melatonin reseptörlerinin rolü
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Dosyalar
Tarih
2017
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Bu tez çalışmasının amacı, in vitro mesane kasılmaları üzerine melatonin reseptörlerinin olası etkilerinin ve bu etkilerin meydana gelmesinde reseptör agonist ve antagonistinin rollerinin araştırılmasıdır. Yöntem: Deneysel çalışmalar, Necmettin Erbakan Üniversitesi KONÜDAM Deneysel Tıp Araştırma ve Uygulama Merkezi ile Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Fizyoloji Anabilim Dalı Laboratuvarı'nda gerçekleştirildi. Çalışmada Wistar cinsi 5-6 aylık, 200–250 g arası 24 adet dişi sıçan kullanıldı. Eter sedasyonunu takiben servikal dislokasyon yöntemi ile sıçanlar ötenazi edildi. Abdomen medyan hattan açılarak mesane çıkarıldı ve Krebs solüsyonu içine alındı. Mesane boyun kısmından apex yönünde longitudinal bir kesi ile açılarak mesaneden vertikal yönde 2X10 mm ebadında iki kas şeridi hazırlandı. Şeritler izole organ banyosundaki cam hazneler içerisindeki düzeneğe 1 g gerim uygulanarak yerleştirildi. Kas şeritlerine melatonin, melatonin reseptör agonist ve antagonisti ve bunların çözücüleri kümülatif olarak uygulandı. 45 dakikalık bir uyum periyodunu takiben spontan kasılma gösteren bütün mesane şeritlerine 10-5 M asetilkolin (ACh) uygulanarak kasılmalar indüklendi. Kümülatif olarak agomelatin (10-8 M-10-3 M), melatonin (0.01 mM, 0.1 mM, 1 mM, 2.5 mM) ve melatonin 2 reseptör antagonisti 4PPDOT (0.01 mM, 0.1 mM) uygulamaları yapıldı ve genlik üzerinde oluşan etkiler kayıt altına alındı. Bulgular: Agomelatin 10-8 M-10-5 M doz aralığında uygulanmasıyla önemli bir etki oluşmazken, 10-4 M ve 10-3 M dozlarında istatistiksel olarak anlamlı bir inhibisyon gözlendi (p<0.01 ve p<0.001, sırasıyla, n=7). Melatonin benzer şekilde, 0.01 mM ve 0.1 mM dozlarının ACh ile indüklenen mesane düz kas kontraksiyonları üzerine etkili olmadığı fakat 1 mM ve 2.5 mM dozlarda kontraksiyonları kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde azalttığı belirlendi (p<0.001). 0,01 mM ve 0.1 mM 4P-PDOT ise 2 mM melatonin uygulanmasıyla oluşan inhibisyonu geri döndürmedi. Sonuç: Agomelatin ve melatonin in vitro sıçan mesane düz kas kontraksiyonları üzerinde belirgin inhibitör etki göstermektedir. Bu etkiler doz bağımlı olarak ortaya çıkmaktadır. Ancak 4P- PDOT in vitro sıçan mesane düz kas kontraksiyonlarını etkilememektedir. Bu da mesane kasılmaları üzerindeki melatoninin oluşturduğu inhibisyonun muhtemelen melatonin 2 reseptörü aracılı olarak ortaya çıkmadığını göstermektedir.
Aim: The objective of this thes is was to investigate the possible effects of melatonin receptors on bladder contractions in vitro and roles of agonist and antagonist in emergence of these effects. Method: Experimental studies were carried out in KONUDAM Experimental Medicine Research and Application Center and the Laboratory of Physiology Department in Necmettin Erbakan University. 24 female Wistar rats (5-6 mount age) weighing 200-250 g have been used in this study. Rats were euthanized by cervical dislocation after light ether sedation. The abdomen was opened by median line and the bladder was removed and taken into the Krebs solution. The bladder was opened with a longitudinal incision in the direction of the apex from the neck to prepare two muscular strips of 2x10 mm in the vertical direction. The strips were placed by applying 1 g of tension to the assembly in the isolated organ bath. Melatonin, melatonin receptor agonist and antagonist and their solubilizers were cumulatively applied to the muscles trips in organ bath. Following a 45-minute equal ibrati on period, tonic contractions were induced by application of acethylcholin (ACh) at 10-5 M concentration. Agomelatin (10-8 M-10-3 M), melatonin (0.01 mM, 0.1 mM, 1 mM, 2.5 mM) and 4PPDOT (a selective melatonin receptor 2 antagonist, 0.01 mM, 0.1 mM) were applied and the effects on contraction amplitudes were recorded. Results: Agomelatin had no effect between 10-8 M and 10-5 M level but there was significant inhibitory effect at the other doses (p<0.01 and p<0.001 respectively, n=7). Similarly, there was no significant effect on bladder smooth muscle contractions after application of 0.01 mM and 0.1 mM melatonin concentrations, whereas melatonin administration both 1 mM and 2.5 mM significantly inhibited the contraction compared to control (p<0.001). 4P-PDOT administration at 0.01 and 0.1 mM concentrations failed to reverse the inhibition occured by 2 mM melatonin application. Conclusion: Agomelatin and melatonin have significant inhibitory effects on rat bladder smooth muscle contractions in vitro. These effects are dose-dependent. However, 4P-PDOT does not have a significant effect on rat bladder smooth muscle contractions. These results show that the inhibition of melatonin on bladder contraction is not mediated by melatonin 2 receptor.
Aim: The objective of this thes is was to investigate the possible effects of melatonin receptors on bladder contractions in vitro and roles of agonist and antagonist in emergence of these effects. Method: Experimental studies were carried out in KONUDAM Experimental Medicine Research and Application Center and the Laboratory of Physiology Department in Necmettin Erbakan University. 24 female Wistar rats (5-6 mount age) weighing 200-250 g have been used in this study. Rats were euthanized by cervical dislocation after light ether sedation. The abdomen was opened by median line and the bladder was removed and taken into the Krebs solution. The bladder was opened with a longitudinal incision in the direction of the apex from the neck to prepare two muscular strips of 2x10 mm in the vertical direction. The strips were placed by applying 1 g of tension to the assembly in the isolated organ bath. Melatonin, melatonin receptor agonist and antagonist and their solubilizers were cumulatively applied to the muscles trips in organ bath. Following a 45-minute equal ibrati on period, tonic contractions were induced by application of acethylcholin (ACh) at 10-5 M concentration. Agomelatin (10-8 M-10-3 M), melatonin (0.01 mM, 0.1 mM, 1 mM, 2.5 mM) and 4PPDOT (a selective melatonin receptor 2 antagonist, 0.01 mM, 0.1 mM) were applied and the effects on contraction amplitudes were recorded. Results: Agomelatin had no effect between 10-8 M and 10-5 M level but there was significant inhibitory effect at the other doses (p<0.01 and p<0.001 respectively, n=7). Similarly, there was no significant effect on bladder smooth muscle contractions after application of 0.01 mM and 0.1 mM melatonin concentrations, whereas melatonin administration both 1 mM and 2.5 mM significantly inhibited the contraction compared to control (p<0.001). 4P-PDOT administration at 0.01 and 0.1 mM concentrations failed to reverse the inhibition occured by 2 mM melatonin application. Conclusion: Agomelatin and melatonin have significant inhibitory effects on rat bladder smooth muscle contractions in vitro. These effects are dose-dependent. However, 4P-PDOT does not have a significant effect on rat bladder smooth muscle contractions. These results show that the inhibition of melatonin on bladder contraction is not mediated by melatonin 2 receptor.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Agomelatin, Melatonin, Mesane, Sıçan, 4P-PDOT, Bladder, Rat
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Takı, F. N. (2017). İn vitro sıçan mesane kasılmaları üzerine melatonin reseptörlerinin rolü. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Fizyoloji Anabilim Dalı, Konya.
