İZOLE SIÇAN MİYOMETRİYUMUNDA METABOLİK İNHİBİSYONA BAĞLI KONTRAKTİL BASKILANMADA FOSFOKREATİN/ KREATİN KİNAZ ENERJİ SİSTEMİNİN ROLÜNÜN İNCELENMESİ

Yıl 2008, Cilt: 7 Sayı: 1, 78 - 83, 30.11.2008

Mete Özcan Ergül Alçın Tuğrul Kuzgun Ahmet Ayar

Öz

Bu
çalışmada, izole sıçan miyometriyumunda, kasılabilirlik yönünden hipoksiye
adaptasyon kapasitesinde Kreatin kinaz (CK)/fosfokreatin (PCr) enerji sisteminin olası rolünün incelenmesi
amaçlanmıştır.

 

Gebe
olmayan erişkin Wistar cinsi dişi sıçanlardan izole edilen miyometriyum
kesitleri, izole organ banyosu-na yerleştirildi ve test ajanları eklenerek;
kontraksiyonların frekansı, amlitüd ve kasılma gücü üzerine olan etkileri, 10
dakikalık periyotlar süresince, veriler normalize edilerek değerlendirildi.
Bulguların istatistiksel değerlendirilmesinde ANOVA varyans analizi testi
kullanıldı.

 

KCN
(0.5mM) ile oluşturulan metabolik stres, spontan kontraksiyonları kademeli
başlayan bir etki ile tama-men inhibe etti. Kasılma eğrisi altında kalan alan
(spontan %100 ), KCN uygulamasını takiben %51.2±9.6 oranında baskılarken; PCr (5 mM) uygulamasını takiben
kontrol değerlerinin %58.4±7.6 (p > 0.05 n=7), CK uygulamasını takiben ise
%62± 7.2 (p > 0.05, n=7) düzeyine kadar derlendi.

 

CK/PCr
enerji sisteminin, metabolik inhibisyona bağlı miyometriyum kasılma gücünde
meydana gelen zayıflamaya kısmen aracılık ettiğini, ancak bunun kasılmayı
sekteye uğratan tek sorumlu mekanizma olmadığını düşündürmektedir.

Anahtar Kelimeler

Miyometriyum, Kasılma, Metabolik Stres, Kretin Kinaz, Rat

Kaynakça

• 1. Bessman, S.P.1985. The Creatine-Creatine Phosphate Energy Shuttle. Annu Rev Biochem. 54, 831-862.
• 2. Clark, J.F., Khuchua, Z., Kuznetsov, A., Saks, V.A. and Ventura-Clapier, R.1993. Compart-mentation of Creatine Kinase Isoenzymes in Myometrium of Gravid Guinea-pig. J Physiol 466, 553-572.
• 3. Dawson, M.J. And Wray, S. 1985. The Effects of Pregnancy and Parturition on Phosphorus Metabolites in Rat Uterus Studied by 31p Nuc-lear Magnetic Resonance. J Physiol 368, 19-31.
• 4. Dupuis, Y., Tardivel, S., Lacour, B. and Fourner,P. 1992. Modulation of Ileal Calcium Transport by Phosphate-Exchanging Compound. Miner Electrolyte Metab 18,61-68.
• 5. Earley, L., Wray S. 1993.The Effects of Hypoxia on Fore Produced by Agonists and Depolariza-tion Arising Spontaneously in the Rat Uterus. J Reprod Fer. 539-544.
• 6. Hardin,C.D., Wiseman, R.W. And Kushmerick, M.J. 1992. Vascular Oxidative Metabolism Under Different Metabolic Conditions. Biochi-mica et Biophysica Acta. 1133, 133-141.
• 7. Harrison, N., Larcombe-McDouall, J.B., Earley, L., And Wray, S. 1994. An in vivo Study of The Effects of Ischemia on Uterine Contraction, Intracellular pH and Metabolites in the Rat. J Physiol. 476,349-54.
• 8. Harrison, N., Larcombe-McDoull, J.B. And Wray, S. 1995. A 31P NMR Investigation into the Effects of Repeated Vascular Occlusion on Uterine Metabolites, Intracellular pH and Force, in vivo. NMR Biomed. 8(1),28-32.
• 9. Ishida, Y., Paul, R. J. 1990. Effects of Hypoxia on High-Energy Phosphagen Content, Energy Metabolites and Isometric Force in Guinea-pig Taenia Caeci. J Physiol 424,41-56.
• 10. Ishida, Y., Wyss, M., Hemmer, W., and Wallimann, N.T. 1991. Identification of Creatine Kinase Isoenzymes in the Guinea-pig. Presence of Mitochondrial Creatine Kinase in Smooth Muscle. FEBS Letters. 283, 37-43.
• 11. Kay L., Nicolay K., Wieringa B., Saks V. And Wallimann T. 2000. Direct Evidence fort he Control of Mitochondrial Respiration by Mitoc-hondrial Creatine Kinase in Oxidative Muscle Cells in situ. J Biol Chem. 275, 6937-6944.
• 12. Konorev, E.A., Medvedea, N.V., Jalilashvili, I.V., Lakomkin, V.L. And Saks, V.A.1991. Participation of Calcium Ions in the Molecular Mechanism of Cardioprotective Action of Exogenous Phosphocreatine. Basic Res Cardiol. 86, 327-339.
• 13. Minajeva, A., Ventura-Clapier, R. And Veksler V. 1996. Ca Uptake by Cardiac Sacoplasmic Reticulum ATPase in situ Strongly Depends on Bound Creatine Kinase. Pflugers Arch. 432, 904-912.
• 14. Nakayama, S., Clark, JF. 2003. Smooth muscle and NMR review: an overview of smooth muscle metabolism. Mol Cell Biochem. 244(1-2):17-30.
• 15. Nakayama, S., Tomita, T. 1990. Depletion of intracellular free Mg2+ in Mg2+- ND Ca2+- free Solution in the Taenia the Isolated from Guine-pig caecum. J Physiol. 421,363-378.
• 16. Nishimura, J., Van Bremen, C. 1991. Energetic Aspects of the Regulation of Ca2+ Sensitivity of Permeabilized rabbit Mesenteric Artery: Possib-le Involvement of a Second Ca2+ Regulatory System in Smooth Muscle Contraction. J Pharmacol Exper Ther. 258, 397-402.
• 17. Parrat, J., Taggart, M. And Wray, S. 1994. Abolition of Contractions in the Myometrium by Acidification in vitro. Lancet. 10(344), 717-8.
• 18. Saks, V.A., Khuchua, Z.A., Vasilyeva, E.V., Belikova, O.Y. and Kuznetsov, A.V. 1994. Metabolic Compartmentation and Substrate Channeling in Muscle Cells. Role of Coupled Creatine Kinases in vivo Regulation of Cellular Respiration: a synthesis. Moll Cell Biochem. 133,155-192.
• 19. Thomas, P.J., Fry, C.H. 1996. The Effects of Cellular Hypoxia Contraction and Extracellular Ion Accumulation in Isolated Human Detrusor Smooth Muscle. J Urol.155, 726-731.
• 20. Ventura-Clapier,R.,Veksler,V.And Hoerter, J. A. 1994 Myofibrillar Creatine Kinase and Cardiac Contraction. Moll Cell Biochem. 133, 125-144.
• 21. Wallimann, T., Wyss, M., Brddiczka, D., Nico-lay, K. And Eppenberger, H. M. 1992. Intracel-lular Compartmentation, Structure and Function of Creatine Kinase Isoenzymes in Tissues With High and Fluctuating Energy Demands: the ‘Phosphocreatine Circuit’ for Cellular Energy Homeostasis. Biochem J. 281, 21-40.
• 22. Wray, S., Duggins, K., Iles, R., Nyman, L., Osman, V. 1992. The Effects of Metabolic Inhibition and Acidification on Force Production in the Rat Uterus. Exp Physiol. 77, 307-319.
• 23. Yoshizaki, K.,Watari, H. And Radda, G.K. 1990. Role of Phosphocreatine in Energy Transport in skeletal Transport in Skeletal Muscle of Bullfrog Studied by 31P-NMR. Biochimica et Biophysi-ca Acta. 1051, 144-150.