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    • Reference Type: Journal Article Record Number: 143 Author: Moro, C. and Chess-Williams, R. Year: 2012 Title: Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder Journal: Auton Autacoid Pharmacol Volume: 32 Issue: 3 Pt 4 Pages: 53-9 Epub Date: 2012/09/22 Date: Oct Short Title: Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder Alternate Journal: Autonomic & autacoid pharmacology ISSN: 1474-8665 DOI: 10.1111/aap.12000 Accession Number: 22994938 Keywords: Abattoirs Acetylcholine/antagonists & inhibitors/physiology Adenosine Triphosphate/antagonists & inhibitors/physiology Animals Electric Stimulation In Vitro Techniques Mucous Membrane/drug effects/*innervation/metabolism *Muscle Contraction/drug effects Muscle, Smooth/drug effects/*innervation/metabolism Nerve Tissue Proteins/antagonists & inhibitors/metabolism Neurons/drug effects/metabolism/*secretion Neurotransmitter Agents/pharmacology Nitric Oxide/antagonists & inhibitors/physiology Norepinephrine/antagonists & inhibitors/physiology Parasympatholytics/pharmacology Receptors, Neurotransmitter/antagonists & inhibitors/metabolism Sus scrofa *Synaptic Transmission/drug effects Tetrodotoxin/pharmacology Urinary Bladder/drug effects/*innervation/metabolism Urothelium/drug effects/*innervation/metabolism Abstract: Acetylcholine, and to a lesser extent ATP, mediates neurogenic contractions of bladder smooth muscle. Recently, the urothelium and lamina propria have also been shown to have contractile properties, but the neurotransmitters involved in mediating responses to nerve stimulation have not been investigated. Isolated strips of porcine urothelium with lamina propria were electrically field stimulated and contractions recorded. Drugs interfering with neurotransmission were then employed to identify which neurotransmitters mediated responses. Strips of urothelium/lamina propria developed spontaneous contractions with a frequency of 3.5+/-0.1 cycles min(-)(1) and amplitude of 0.84+/-0.06 g. Electrical field stimulation at 5, 10, and 20 Hz resulted in frequency-related contractions (1.13+/-0.36 g, 1.59+/-0.46 g and 2.20+/-0.53 g, respectively, n=13), and these were reduced in the presence of tetrodotoxin (1 mum) by 77+/-20% at 5 Hz, 79+/-7% at 10 Hz and 74+/-12% at 20 Hz (all P<0.01), indicating they were predominantly neurogenic in nature. Neither the muscarinic antagonist atropine (10 mum), the adrenergic neurone blocker guanethidine (10 mum) nor desensitization of the purinergic receptors with alpha,beta-methylene ATP (10 mum) affected the contractile amplitude. Similarly, responses were not affected by the nitric oxide synthase inhibitor L-NNA (100 mum) or drugs that interfere with peptide neurotransmission (capsaicin, NK2 antagonist GR159897, protease inhibitors). In conclusion, electrical depolarization of the nerves present in the porcine urothelium/lamina propria results in frequency-dependent contractions, which are predominantly neurogenic in nature. These contractions are resistant to drugs that inhibit the adrenergic, cholinergic and purinergic systems. The neurotransmitter involved in the responses of this tissue is therefore unknown but does not appear to be a peptide. Notes: 1474-8673 Moro, C Chess-Williams, R Journal Article Research Support, Non-U.S. Gov't England Auton Autacoid Pharmacol. 2012 Oct;32(3 Pt 4):53-9. doi: 10.1111/aap.12000. Author Address: Faculty of Health Sciences and Medicine, Bond University, Queensland, 4229, Australia. Caption: 1473133270 Database Provider: NLM Language: eng Reference Type: Journal Article Record Number: 139 Author: Moro, C., Edwards, L. and Chess-Williams, R. Year: 2016 Title: 5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria Journal: Int J Urol Epub Date: 2016/08/18 Date: Aug 16 Short Title: 5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria Alternate Journal: International journal of urology : official journal of the Japanese Urological Association ISSN: 0919-8172 DOI: 10.1111/iju.13172 Accession Number: 27531585 Keywords: 5-hydroxytryptamine bladder lamina propria serotonin urothelium Abstract: OBJECTIVES: To examine the effect of 5-hydroxytryptamine (5-HT; serotonin) on the contractile properties of the urothelium and lamina propria, as a better understanding of bladder physiology might aid the development of new treatments. METHODS: Strips of porcine urothelium and lamina propria were suspended in gassed Krebs-bicarbonate solution, and cumulative concentration-response curves for 5-HT were generated in the absence and presence of 5-HT antagonists, Nomega-nitro-l-arginine and indomethacin. Responses to alpha-methyl-5-HT were also examined. RESULTS: Strips of urothelium/lamina propria developed spontaneous contractions, whereas the addition of 5-HT induced concentration-dependent increases in contractile tone with maximal contractions of 50.43 +/- 2.78 mN/g tissue weight (n = 100). Tonic contractions to 5-HT were unchanged in the presence of Nomega-nitro-l-arginine (100 mumol/L) or indomethacin (5 mumol/L). Selective concentrations of the antagonists methiothepin (5-HT1&2 , 100 nmol/L), RS102221 (5-HT2C , 30 nmol/L), ondansetron (5-HT3 , 30 nmol/L), GR113808, (5-HT4 , 100 nmol/L), SB699551 (5-HT5 , 10 nmol/L), SB399885 (5-HT6 , 100 nmol/L) and SB269970 (5-HT7 , 10 nmol/L) did not influence responses to 5-HT. However, the 5-HT2A antagonist, ketanserin (30-300 mumol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9. CONCLUSIONS: The results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor. Notes: 1442-2042 Moro, Christian Edwards, Lily Chess-Williams, Russ Journal article Int J Urol. 2016 Aug 16. doi: 10.1111/iju.13172. Author Address: Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia. Caption: 1472688944 Database Provider: NLM Language: Eng Reference Type: Journal Article Record Number: 144 Author: Moro, C., Leeds, C. and Chess-Williams, R. Year: 2012 Title: Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide Journal: Eur J Pharmacol Volume: 674 Issue: 2-3 Pages: 445-9 Epub Date: 2011/11/29 Date: Jan 15 Short Title: Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide Alternate Journal: European journal of pharmacology ISSN: 0014-2999 DOI: 10.1016/j.ejphar.2011.11.020 Accession Number: 22119378 Keywords: Animals Carbachol/pharmacology Dose-Response Relationship, Drug Electric Stimulation In Vitro Techniques Mucous Membrane/cytology/drug effects/physiology Muscle Contraction/*drug effects Nitric Oxide/*pharmacology Swine Urinary Bladder/cytology/*drug effects/*physiology Urothelium/cytology/*drug effects/*physiology Abstract: In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 +/- 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(omega)-nitro-l-arginine (L-NNA, 100 muM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 muM) and nitroprusside (10 muM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 +/- 4% (P<0.001) and 35 +/- 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue. Notes: 1879-0712 Moro, Christian Leeds, Charlotte Chess-Williams, Russ Journal Article Research Support, Non-U.S. Gov't Netherlands Eur J Pharmacol. 2012 Jan 15;674(2-3):445-9. doi: 10.1016/j.ejphar.2011.11.020. Epub 2011 Nov 19. Author Address: Department of Biomedical Science, Bond University, Queensland 4229, Australia. Caption: 1473133270 Database Provider: NLM Language: eng Reference Type: Journal Article Record Number: 142 Author: Moro, C., Tajouri, L. and Chess-Williams, R. Year: 2013 Title: Adrenoceptor function and expression in bladder urothelium and lamina propria Journal: Urology Volume: 81 Issue: 1 Pages: 211.e1-7 Epub Date: 2012/12/04 Date: Jan Short Title: Adrenoceptor function and expression in bladder urothelium and lamina propria Alternate Journal: Urology ISSN: 0090-4295 DOI: 10.1016/j.urology.2012.09.011 Accession Number: 23200975 Keywords: Adrenergic alpha-1 Receptor Agonists/pharmacology Adrenergic alpha-1 Receptor Antagonists/pharmacology Adrenergic alpha-Agonists/pharmacology Adrenergic beta-Agonists/pharmacology Adrenergic beta-Antagonists/pharmacology Animals Gene Expression/*drug effects In Vitro Techniques Mucous Membrane/drug effects/metabolism/physiology Muscle Contraction/*drug effects Norepinephrine/pharmacology Receptors, Adrenergic, alpha-1/*genetics/metabolism Receptors, Adrenergic, beta/*genetics/metabolism Swine Urinary Bladder/drug effects/*metabolism/physiology Urothelium/drug effects/*metabolism/physiology Abstract: OBJECTIVE: To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria). MATERIALS AND METHODS: The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes. RESULTS: The tissues expressed all alpha1- and beta-adrenoceptor subtypes, with the alpha1A-, alpha1B-, and beta2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the alpha1-adrenoceptor agonists phenylephrine (100 muM) and A61603 (10 muM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 muM). In contrast, isoprenaline and salbutamol (both 1 muM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM). CONCLUSION: Although all alpha1- and beta-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the alpha1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The beta-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by beta2-adrenoceptors, with beta1- and beta2-adrenoceptors possibly involved in the tension responses. Notes: 1527-9995 Moro, Christian Tajouri, Lotti Chess-Williams, Russ Journal Article Research Support, Non-U.S. Gov't United States Urology. 2013 Jan;81(1):211.e1-7. doi: 10.1016/j.urology.2012.09.011. Epub 2012 Nov 30. Author Address: Bond Urology Group, Bond University Faculty of Health Sciences and Medicine, Gold Coast, Queensland, Australia. Caption: 1473133270 Database Provider: NLM Language: eng Reference Type: Journal Article Record Number: 145 Author: Moro, C., Uchiyama, J. and Chess-Williams, R. Year: 2011 Title: Urothelial/lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol Journal: Urology Volume: 78 Issue: 6 Pages: 1442.e9-15 Epub Date: 2011/10/18 Date: Dec Short Title: Urothelial/lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol Alternate Journal: Urology ISSN: 0090-4295 DOI: 10.1016/j.urology.2011.08.039 Accession Number: 22001099 Keywords: Animals Atropine/pharmacology Benzhydryl Compounds/pharmacology Benzofurans/pharmacology Carbachol/*pharmacology Cresols/pharmacology Diamines/pharmacology Mandelic Acids/pharmacology Mucous Membrane/drug effects/metabolism Muscarinic Antagonists/*pharmacology *Muscle Contraction/drug effects Phenylpropanolamine/pharmacology Piperidines/pharmacology Pirenzepine/pharmacology Pyrrolidines/pharmacology Quinuclidines/pharmacology Receptor, Muscarinic M3/*metabolism Solifenacin Succinate *Stress, Mechanical Swine Tetrahydroisoquinolines/pharmacology Tolterodine Tartrate Urinary Bladder/drug effects/*metabolism Urothelium/drug effects/*metabolism Abstract: OBJECTIVE: To investigate the effects of tissue stretch and muscarinic receptor stimulation on the spontaneous activity of the urothelium/lamina propria and identify the specific receptor subtype mediating these responses. METHODS: Isolated strips of porcine urothelium with lamina propria were set up for in vitro recording of contractile activity. Muscarinic receptor subtype-selective antagonists were used to identify the receptors influencing the contractile rate responses to stretch and stimulation with carbachol. RESULTS: Isolated strips of urothelium with lamina propria developed spontaneous contractions (3.7 cycles/min) that were unaffected by tetrodotoxin, Nomega-nitro-L-arginine, or indomethacin. Carbachol (1 muM) increased the spontaneous contractile rate of these tissue strips by 122% +/- 27% (P < .001). These responses were significantly depressed in the presence of the M3-selective muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (10-30 nM) but were not affected by the M1-selective antagonist pirenzepine (30-100 nM) or the M2-selective antagonist methoctramine (0.1-1 muM). Stretching of the tissue also caused an increase in the spontaneous contractile rate, and these responses were abolished by atropine (1 muM) and low concentrations of 4-diphenylacetoxy-N-methylpiperidine methiodide (10 nM). Darifenacin, oxybutynin, tolterodine, and solifenacin (1 muM) all significantly depressed the frequency responses to carbachol (1 muM). CONCLUSION: The urothelium with the lamina propria exhibits a spontaneous contractile activity that is increased during stretch. The mechanism appears to involve endogenous acetylcholine release acting on M3 muscarinic receptors. Anticholinergic drugs used clinically depress the responses of these tissues, and this mechanism might represent an additional site of action for these drugs in the treatment of bladder overactivity. Notes: 1527-9995 Moro, Christian Uchiyama, Jumpei Chess-Williams, Russ Journal Article Research Support, Non-U.S. Gov't United States Urology. 2011 Dec;78(6):1442.e9-15. doi: 10.1016/j.urology.2011.08.039. Epub 2011 Oct 15. Author Address: Department of Biomedical Science, Bond University Faculty of Health Sciences and Medicine, Queensland, Australia. Caption: 1473133270 Database Provider: NLM Language: eng
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