Investigation of Intracellular Mechanisms of Sphingosine-1-Phosphate (S1P)-Induced Contractions in Detrusor Smooth Muscle of Rats having Cyclophosphamide-Induced Cystitis

Anjum I., Investigation of Intracellular Mechanisms of Sphingosine-1-Phosphate (S1P)-Induced Contractions in Detrusor Smooth Muscle of Rats having Cyclophosphamide-Induced Cystitis, Hacettepe University, Institute of Health Sciences, Doctor of Philosphy in Pharmacology, Ankara 2017. Interstitial cystitis is a chronic disease characterized by lower abdominal pain and an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P1-3 receptors). The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. S1P-induced contraction and calcium sensitization response were significantly increased in cystitis. According to our data, both S1P2 and S1P3 receptors are involved in S1P-induced augmented contractile response. Both Rho kinase (ROCK) and protein kinase C (PKC) pathways of calcium sensitization play a role in that increase. Furthermore, sarcoplasmic reticulum calcium stores and calcium storing lysosome-related organelles participate in S1P-induced contraction. The investigation of intracellular mechanisms of mediators which has a role in detrusor innervation under pathologic conditions may be of importance in developing new drugs for the treatment of bladder dysfunction. Key words: Sphingosine 1-phosphate, cystitis, permebilized, detrusor smooth muscle, rat ; Anjum İ., Siklofosfamid ile sistit oluşturulan sıçanların detrusor düz kasında sfingosin 1-fosfat (S1P) ile indüklenen kasılma yanıtlarının mekanizmasının incelenmesi, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü Farmakoloji Programı Doktora Tezi, Ankara 2017. İnterstisyel sistit abdominal ağrı ve işeme sıklığı ve aciliyetinde artış ile karakterize kronik bir hastalıktır. Sfingosin 1-fosfat (S1P), G-protein kenetli reseptörler (S1P1-3 reseptörler) aracılı düz kas tonusunu kontrol eden bir biyoaktif sfingolipiddir. Bu tez ...