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

Abstract

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