ryanodine and Cystitis--Interstitial

Interstitial cystitis is a syndrome characterized by detrusor overactivity and chronic inflammation of the bladder. The mechanisms responsible for the altered smooth muscle contractility remain poorly understood. The aim of the study was to investigate the role of intracellular signalling pathways in carbachol-induced detrusor contraction in a rat model of interstitial cystitis. Cyclophosphamide (150 mg/kg, dissolved in saline) was injected to rats (Sprague-Dawley, female, 200-250 g) intraperitoneally once a day on days 1, 4 and 7 to induce interstitial cystitis. Control groups were injected with saline (0.9% NaCl). Detrusor smooth muscle strips were mounted in 1-ml organ baths containing HEPES-buffered modified Krebs' solution and permeabilized with 40 μM β-escin for 30 min. Carbachol-induced contractions were significantly increased from 21.2 ± 1.6% (saline-treated) to 44 ± 4.4% in cyclophosphamide-treated group. The Rho kinase inhibitor Y-27632 (8.8 ± 2%) and the protein kinase C inhibitor GF-109203X (11.7 ± 2.8%) inhibited the increased contractile response (44 ± 4.4%) in rats with cystitis. The increased carbachol-induced contraction (44 ± 4.4%) was also significantly inhibited by the sarcoplasmic reticulum ryanodine channel blocker ryanodine (25.8 ± 3.2%) and the sarcoplasmic reticulum IP

Topics: Amides; Animals; Carbachol; Cholinergic Agonists; Cystitis, Interstitial; Enzyme Inhibitors; Heparin; Indoles; Inositol 1,4,5-Trisphosphate Receptors; Maleimides; Muscle Contraction; Muscle Relaxants, Central; Protein Kinase C; Pyridines; Rats; rho-Associated Kinases; rhoA GTP-Binding Protein; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Signal Transduction; Urinary Bladder