A5047216342- Urinary Bladder and Prostate Research
- Pelvic floor disorders treatments
- Urological Disorders and Treatments
- Adenosine and Purinergic Signaling
- Neuroscience and Neural Engineering
- Neuroscience of respiration and sleep
- Ion Channels and Receptors
- Pain Mechanisms and Treatments
- Connexins and lens biology
- Muscle activation and electromyography studies
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neonatal Health and Biochemistry
- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Tissue Engineering and Regenerative Medicine
- Retinopathy of Prematurity Studies
- Anesthesia and Sedative Agents
- Pain Management and Treatment
- Neuropeptides and Animal Physiology
- Anesthesia and Pain Management
- Calcium signaling and nucleotide metabolism
- Neurological disorders and treatments
- Neuroendocrine regulation and behavior
- EEG and Brain-Computer Interfaces
University of Pittsburgh
2016-2025
University of Pennsylvania
2011-2020
Institute of Cell Biology and Neurobiology
2012
Laboratoire de Biophotonique et Pharmacologie
2012
National Yang Ming Chiao Tung University
2001
Kaohsiung Chang Gung Memorial Hospital
2001
In mammals, the bladder stores urine without permitting passage of contents into bloodstream, a function, in part, uroepithelial-associated tight junction complex. The protein constituents that make up this high-resistance barrier are currently unknown, although claudins, multigene family, thought to govern paracellular transport other epithelia. Reverse transcriptase-polymerase chain reaction analysis was used define mRNA for claudin-2, -4, -8, -12, and -13 expressed mouse tissue....
Mechanical deformation produces complex effects on neuronal systems, some of which can lead to dysfunction and death. While astrocytes are known respond mechanical forces, it is not clear whether neurons also directly. We examined mechanosensitive ATP release the physiological response this in isolated retinal ganglion cells. Purified cells released upon swelling. Release was blocked by carbenoxolone, probenecid or peptide (10)panx, implicating pannexin channels as conduits. stretch...
As adenosine 5′‐triphosphate (ATP) released from astrocytes can modulate many neural signaling systems, the triggers and pathways for this ATP release are important. Here, ability of mechanical strain to trigger through pannexin channels effects sustained on expression were examined in rat optic nerve head astrocytes. Astrocytes when subjected 5% equibiaxial or hypotonic swelling. Although expressed mRNA pannexins 1–3, connexin 43, VNUT, pharmacological analysis suggested a predominant role...
Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune and can link insult to chronic inflammation. requires two stages contribute: priming activation. stage involves upregulation components while activation results assembly complex. step be rate limiting connect inflammation, but our knowledge signals that regulate sterile...
The mechanisms that link visceral mechanosensation to the perception of internal organ status (i.e., interoception) remain elusive. In response bladder filling, urothelium releases ATP, which is hypothesized stimulate voiding function by communicating degree fullness subjacent tissues, including afferent nerve fibers. To determine if PIEZO channels as mechanosensors in these events, we generated conditional urothelial Piezo1-, Piezo2-, and dual Piezo1/2-knockout (KO) mice. While functional...
The bladder urothelium exhibits dynamic sensory properties that adapt to changes in the local environment. These studies investigated localization and function of bradykinin receptor subtypes B1 B2 normal inflamed (cyclophosphamide (CYP)-induced cystitis) their contribution lower urinary tract rat. Our findings indicate 2 (B2R) but not 1 (B1R) is expressed control urothelium. B2R immunoreactivity was localized throughout bladder, including detrusor smooth muscle. Bradykinin-evoked activation...
Although nicotinic acetylcholine receptors in both the central and peripheral nervous systems play a prominent role control of urinary bladder function, little is known regarding expression or function epithelium, urothelium. Nicotinic have been described epithelial cells lining upper gastrointestinal tract, respiratory skin. Thus present study examined functionality urothelium, as well effects stimulation on micturition reflex. mRNA for α 3 , 5 7 β 4 subunits was identified rat urothelial...
Lysosomal enzymes function optimally at low pH; as accumulation of waste material contributes to cell aging and disease, dysregulation lysosomal pH may represent an early step in several pathologies. Here, we demonstrate that stimulation the P2X7 receptor (P2X7R) for ATP alkalinizes lysosomes cultured human retinal pigmented epithelial (RPE) cells impairs function. P2X7R did not kill RPE but alkalinized by 0.3 U. Receptor also elevated cytoplasmic Ca2+; Ca2+ influx was necessary sufficient...
ATP is released through pannexin channels into the lumen of rat urinary bladder in response to distension or stimulation with bacterial endotoxins. Luminal plays a physiological role control micturition because intravesical perfusion apyrase ecto-ATPase inhibitor ARL67156 altered reflex activity anaesthetized rat. The release from apical and basolateral surfaces urothelium appears be mediated by separate mechanisms administration channel antagonist Brilliant Blue FCF increased capacity,...
Muscarinic receptors (mAChRs) have been identified in the urothelium, a tissue that may be involved bladder sensory mechanisms. This study investigates expression and function of mAChRs using cultured urothelial cells from rat. RT-PCR established all five mAChR subtypes. agonists acetylcholine (ACh; 10 microM), muscarine (Musc; 20 oxotremorine methiodide (OxoM; 0.001-20 microM) elicited transient repeatable increases intracellular calcium concentration ([Ca(2+)](i)) approximately 50% cells....
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead both pro-inflammatory neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine systems is often associated with glial cells like astrocytes microglia, contribution of neurons themselves response underappreciated has bearing on any balanced response....
The control and regulation of the lower urinary tract are partly mediated by purinergic signaling. This study investigated distribution function P2Y receptors in rat bladder. Application agonists to urothelial cells evoked increases intracellular calcium; rank order agonist potency (pEC(50) +/- SE) was ATP (5.10 0.07) > UTP (4.91 0.14) UTPgammaS (4.61 0.16) = ATPgammaS (4.70 0.05) 2-methylthio adenosine 5'-diphosphate 5'-(N-ethylcarboxamido)adenosine ADP (<3.5). for these indicates that...
It has been previously determined that the epithelial lining of urinary bladder, or urothelium, expresses two subtypes nicotinic acetylcholine receptors (nAChRs) mediate distinct physiological effects in vivo. These include inhibition bladder reflexes through α7 and an excitation α3-containing (α3*) receptors. is believed urothelial their modulating release neurotransmitters such as ATP subsequently influence afferent nerve excitability. Therefore, we examined distribution nAChRs well...
Abstract Mechanical strain in neural tissues can lead to the up‐regulation and release of multiple cytokines including interleukin 6 (IL‐6). In retina, mechanosensitive ATP autostimulate P2X7 receptors on both retinal ganglion cell neurons optic nerve head astrocytes. Here, we asked whether purinergic signaling contributed IL‐6 response increased intraocular pressure (IOP) vivo , stretch or swelling vitro . Rat mouse eyes were exposed non‐ischemic elevations IOP 50–60 mmHg for 4 h. A PCR...
Lysosomal dysfunction is associated with a number of age-related pathologies that affect all organ systems. While much research has focused on neurodegenerative diseases and aging-induced changes in neurons, less known about the impact aging lower urinary tract function. Our studies explored age-dependent content endo-lysosomal organelles (i.e., multivesicular bodies, lysosomes, product their fusion, endolysosomes) age-induced effects lysosomal degradation urothelium, epithelial tissue lines...
Cross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers ATP release from both astrocytes retinal pigmented epithelial (RPE) cells. efflux was accompanied by acid phosphatase beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, alkalization with bafilomycin or chloroquine triggered Lysosomal rupture glycyl-L-phenylalanine-2-naphthylamide (GPN)...
While it is well known that the sensory arm of micturition reflex mediated by A-δ afferents in pelvic nerve, urinary bladder also innervated hypogastric nerve (HGN), whose role less understood. We have recently determined stimulation HGN can facilitate nociceptive activity cat induced intravesical instillation acetic acid. The aim present study, then, was to determine if activation could similarly normal cat, evoked saline distension. Additional experiments examined modulate inhibitory...
The afferent limb of the vesicovascular reflex (VV-R) evoked by distension or contraction urinary bladder (UB) was studied in urethane-anesthetized female rats examining changes VV-R after administration C-fiber neurotoxins [capsaicin and resiniferatoxin (RTX)]. Systemic arterial blood pressure increased parallel (5.1 to 53.7 mmHg) with graded increases UB (20 80 cmH 2 O) during contractions. pressor response significantly reduced (60–85%) acute chronic (4 days earlier) intravesical RTX...