187 INTRACELLULAR CALCIUM RESPONSE AND BLADDER CONTRACTIONS EVOKED BY PURINERGIC RECEPTOR ACTIVATION ARE INHIBITED BY NICOTINE IN BLADDER SMOOTH MUSCLE

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2010187 INTRACELLULAR CALCIUM RESPONSE AND BLADDER CONTRACTIONS EVOKED BY PURINERGIC RECEPTOR ACTIVATION ARE INHIBITED BY NICOTINE IN BLADDER SMOOTH MUSCLE Alvaro Munoz, Cristopher P. Smith, Timothy B. Boone, and George T. Somogyi Alvaro MunozAlvaro Munoz More articles by this author , Cristopher P. SmithCristopher P. Smith More articles by this author , Timothy B. BooneTimothy B. Boone More articles by this author , and George T. SomogyiGeorge T. Somogyi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.243AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder smooth muscle contractions are mediated by muscarinic and purinergic receptors. Recent results from our laboratory revealed that in the presence of the mixed muscarinic/nicotinic agonist carbachol the purinergic response is attenuated, raising the possibility that the nicotinic receptor has a depressing role in the regulation of the purinergic response. The objective of the present experiments was to analyze the possible negative interaction of nicotinic/muscarinic with smooth muscle purinergic receptors. METHODS Freshly dissociated rat bladder smooth muscle cells were exposed to fura-2 M and the intracellular levels of calcium were measured with a ratiometric method. The cells were plated on a cover slip and the system was continuously superfused with a HEPES buffered saline solution. Drugs were locally applied with an injection system in 3 min intervals. In separate experiments, rat bladder strips were mounted in an organ bath and the contractile responses were isometrically measured in response to drugs injected into the bath every 15 min. RESULTS Consecutive applications of muscarin (Musc) (50uM) or alpha-beta methylene ATP (mATP) (50uM) increased intracellular calcium levels (ICL) but showed only a small extent of desensitization. Nicotine (50uM) itself also increased ICL but to a lesser extent. However, injecting nicotine and mATP together the calcium level was significantly attenuated by 80% as compared to mATP applied alone. The effect of subsequent application of mATP was higher again indicating that the inhibition is due to nicotinic receptor activation and not purinergic desensitization. Measuring the isometric contractions of bladder strips both Musc and mATP evoked sizable contractions while nicotine was ineffective. However, applying mATP together with nicotine the contractile response was abolished and the inhibition persisted after washout. Subsequent applications of mATP did not exhibit desensitization. CONCLUSIONS In the urinary bladder simultaneous activation of smooth muscle nicotinic and purinergic receptors attenuate ICL and contractile responses. Since the released acetylcholine activates both Musc and nicotinic receptors, the simultaneously released ATP will meet inhibited purinergic receptors and the cholinergic response prevails. Houston, TX© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e74 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alvaro Munoz More articles by this author Cristopher P. Smith More articles by this author Timothy B. Boone More articles by this author George T. Somogyi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...