scholarly journals Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats

2021 ◽  
Vol 14 (10) ◽  
pp. 960
Author(s):  
Wei-Yi Wu ◽  
Shih-Pin Lee ◽  
Bing-Juin Chiang ◽  
Wei-Yu Lin ◽  
Chiang-Ting Chien
Keyword(s):  
Urinary Bladder ◽  
Bladder Smooth Muscle ◽  
Calcium Sensing Receptor ◽  
Efferent Nerve ◽  
Micturition Reflex ◽  
Bladder Urothelium ◽  
Calcium Sensing ◽  
Urinary Bladder Smooth Muscle ◽  
Bladder Disorders

The urothelium displays mechano- and chemosensory functions via numerous receptors and channels. The calcium-sensing receptor (CaSR) detects extracellular calcium and modulates several physiological functions. Nonetheless, information about the expression and the role of CaSR in lower urinary tract has been absent. We aimed to determine the existence of urothelial CaSR in urinary bladder and its effect on micturition function. We utilized Western blot to confirm the expression of CaSR in bladder and used immunofluorescence to verify the location of the CaSR in the bladder urothelium via colocalization with uroplakin III A. The activation of urothelial CaSR via the CaSR agonist, AC-265347 (AC), decreased urinary bladder smooth muscle (detrusor) activity, whereas its inhibition via the CaSR antagonist, NPS-2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities recording, and bladder surface microcirculation detection were conducted to evaluate the effects of the urothelial CaSR via intravesical administrations. Intravesical AC inhibited micturition reflex, bladder afferent and efferent nerve activities, and reversed cystitis-induced bladder hyperactivity. The urothelial CaSR demonstrated a chemosensory function, and modulated micturition reflex via regulating detrusor activity. This study provided further evidence of how the urothelial CaSR mediated micturition and implicated the urothelial CaSR as a potential pharmacotherapeutic target in the intervention of bladder disorders.

In vitro and in vivo relaxation of urinary bladder smooth muscle by the selective myosin II inhibitor, blebbistatin

2011 ◽  
Vol 107 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Xinhua Zhang ◽  
Dwaraka Srinivasa R. Kuppam ◽  
Arnold Melman ◽  
Michael E. DiSanto
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Myosin Ii ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle

Simulation of In Vitro-Like Electrical Activities in Urinary Bladder Smooth Muscle Cells

2017 ◽  
Vol 33 ◽  
pp. 45-51
Author(s):  
Chitaranjan Mahapatra ◽  
Rohit Manchanda
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Neurotransmitter Release ◽  
Compartment Model ◽  
Bladder Smooth Muscle ◽  
Parasympathetic Nerve ◽  
Stochastic Nature ◽  
Urinary Bladder Smooth Muscle ◽  
Electrical Activities

Urinary bladder smooth muscle (UBSM) generates spontaneous electrical activities due to stochastic nature of purinergic neurotransmitter release from the parasympathetic nerve. The stochastic nature of the purinergic neurotransmitter release was represented by a simplified ‘point-conductance’ model to mimic in vitro-like electrical activities in UBSM cell. The point-conductance was represented by the independent synaptic conductance described by the stochastic random-walk processes and injected into a single-compartment model of mouse UBSM cell. This model successfully evoked irregular spontaneous depolarizations (SDs) and spontaneous action potential (sAP) as the properties of in vitro-like electrical activities in UBSM cells. The model mimics the T- and L-type Ca2+ ion channel blocker by setting their respective conductance to zero. We also found that the point-conductance model modulates the sAP properties by adding background activity.

scholarly journals Generation of a cell line with smooth muscle phenotype from hypertrophied urinary bladder

2002 ◽  
Vol 283 (1) ◽  
pp. C373-C382 ◽  
Author(s):  
Yongmu Zheng ◽  
Wilfried T. Weber ◽  
Shuqin Wang ◽  
Alan J. Wein ◽  
Stephen A. Zderic ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Cell Line ◽  
Muscarinic Agonist ◽  
Bladder Smooth Muscle ◽  
Homogeneous Population ◽  
Amino Terminal ◽  
Urinary Bladder Smooth Muscle ◽  
A Cell

We have established a cell line from hypertrophied rabbit urinary bladder smooth muscle (SM) that stably expresses SM myosin (SMM). These cells, termed BSM, are spindle shaped and form swirls, similar to the “hills and valleys” described for cultured aortic SM cells. Western blotting revealed that BSM expresses the amino-terminal SMM heavy chain isoform SM-B, the carboxy-terminal SM1 and SM2 isoforms, and SM α-actin. In addition, they express cGMP-dependent protein kinase G, made by contractile SM cells in vitro but not by noncontractile cells synthesizing extracellular matrix. Immunofluorescence studies indicate a homogeneous population of cells expressing α-actin and SMM, including the SM-B isoform, and karyotyping demonstrates a stable 4N chromosomal pattern. These cells also express calcium-dependent myosin light chain kinase and phosphatase activity and contract in response to the muscarinic agonist bethanechol. To our knowledge, BSM is the first visceral SM cell line that expresses the SM-B isoform and might serve as a useful model to study the transcriptional regulation of tissue-specific SMM isoforms in differentiation and pathological SM.

scholarly journals Stretch-induced Calcium Release in Smooth Muscle

2002 ◽  
Vol 119 (6) ◽  
pp. 533-543 ◽  
Author(s):  
Guangju Ji ◽  
Robert J. Barsotti ◽  
Morris E. Feldman ◽  
Michael I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Smooth Muscle Cells ◽  
Calcium Release ◽  
Muscle Cells ◽  
Intraluminal Pressure ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle ◽  
Inward Currents ◽  
Longitudinal Stretch

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor–mediated Ca2+ release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to ∼120% of slack length (ΔL = 20) evoked Ca2+ release from intracellular stores in the form of single Ca2+ sparks and propagated Ca2+ waves. Ca2+ release was not due to calcium-induced calcium release, as release was observed in Ca2+-free extracellular solution and when free Ca2+ ions in the cytosol were strongly buffered to prevent increases in [Ca2+]i. Stretch-induced calcium release (SICR) was not affected by inhibition of InsP3R-mediated Ca2+ release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca2+ release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

Peptide Blocking Self-Polymerization of Extracellular Calcium-Sensing Receptor Attenuates Hypoxia-Induced Pulmonary Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Rui Xiao ◽  
Shengquan Luo ◽  
Ting Zhang ◽  
Yankai Lv ◽  
Tao Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Disulfide Bonds ◽  
Acute Hypoxia ◽  
Extracellular Domain ◽  
Left Ventricular ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Activation of the CaSR (extracellular calcium-sensing receptor) has been recognized as a critical mediator of hypoxia-induced pulmonary hypertension. Preventive targeting of the early initiating phase as well as downstream events after CaSR activation remains unexplored. As a representative of the G protein-coupled receptor family, CaSR polymerizes on cell surface upon stimulation. Immunoblotting together with MAL-PEG technique identified a reactive oxygen species-sensitive CaSR polymerization through its extracellular domain in pulmonary artery smooth muscle cells upon exposure to acute hypoxia. Fluorescence resonance energy transfer screening employing blocking peptides determined that cycteine129/131 residues in the extracellular domain of CaSR formed intermolecular disulfide bonds to promote CaSR polymerization. The monitoring of intracellular Ca 2+ signal highlighted the pivotal role of CaSR polymerization in its activation. In contrast, the blockade of disulfide bonds formation using a peptide decreased both CaSR and hypoxia-induced mitogenic factor expression as well as other hypoxic-related genes in vitro and in vivo and attenuated pulmonary hypertension development in rats. The blocking peptide did not affect systemic arterial oxygenation in vivo but inhibited acute hypoxia-induced pulmonary vasoconstriction. Pharmacokinetic analyses revealed a more efficient lung delivery of peptide by inhaled nebulizer compared to intravenous injection. In addition, the blocking peptide did not affect systemic arterial pressure, body weight, left ventricular function, liver, or kidney function or plasma Ca 2+ level. In conclusion, a peptide blocking CaSR polymerization reduces its hypoxia-induced activation and downstream events leading to pulmonary hypertension and represents an attractive inhaled preventive alternative worthy of further development.

Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscle

2005 ◽  
Vol 25 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Anita S. Mannikarottu ◽  
Michael E. DiSanto ◽  
Stephen A. Zderic ◽  
Alan J. Wein ◽  
Samuel Chacko
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Thin Filament ◽  
Bladder Smooth Muscle ◽  
Altered Expression ◽  
Associated Proteins ◽  
Urinary Bladder Smooth Muscle

scholarly journals Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle

2003 ◽  
Vol 138 (5) ◽  
pp. 757-766 ◽  
Author(s):  
Alexandra Wibberley ◽  
Zunxuan Chen ◽  
Erding Hu ◽  
J Paul Hieble ◽  
Timothy D Westfall
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Functional Role ◽  
Rho Kinase ◽  
Bladder Smooth Muscle ◽  
Rat Urinary Bladder ◽  
Urinary Bladder Smooth Muscle
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