Anoctamin 1 in secretory epithelia

Jang, Yongwoo; Oh, Uhtaek

doi:10.1016/j.ceca.2014.02.006

Cited by 44 publications

(36 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lack of Ano1-like immunoreactivity in our study is unlikely to be due to issues with antibody-antigen binding, as robust Ano1-immunoreactivity was detected within intestinal tissues and also on the perimetrial surface of the uterus. On the outer serous coat of the uterus, Ano1 channels are likely to serve a secretory role, as has been suggested for airway epithelia, the intestine, kidneys, pancreas and salivary glands [81][82][83][84].…”

Section: -Conductances and Uterine Pacemaker Eventsmentioning

confidence: 90%

Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade1

Dodds

Staikopoulos

Beckett

2015

Biology of Reproduction

View full text Add to dashboard Cite

Mechanisms involved in the generation of spontaneous uterine contractions are not fully understood. Kit-expressing interstitial cells of Cajal are pacemakers of contractile rhythm in other visceral organs, and recent studies describe a role for Ca(2+)-activated Cl(-) currents as the initiating conductance in these cells. The existence and role of similar specialized pacemaker cells in the nonpregnant uterus remains undetermined. Spontaneous contractility patterns were characterized throughout the estrous cycle in isolated, nonpregnant mouse uteri using spatiotemporal mapping and tension recordings. During proestrus, estrus, and diestrus, contraction origin predominated in the oviduct end of the uterus, suggesting the existence of a dominant pacemaker site. Propagation speed of contractions during estrus and diestrus were significantly slower than in proestrus and metestrus. Five major patterns of activity were predominantly exhibited in particular stages: quiescent (diestrus), high-frequency phasic (proestrus), low-frequency phasic (estrus), multivariant (metestrus), and complex. Kit-immunopositive cells reminiscent of pacemaking ICCs were not consistently observed within the uterus. Niflumic acid (10 μM), anthracene-9-carboxylic acid (0.1-1 mM), and 5-nitro-2-(3-phenylpropylamino)benzoic acid (10 μM) each reduced the frequency of spontaneous contractions, suggesting involvement of Cl(-) channels in generating spontaneous uterine motor activity. It is unlikely that this conductance is generated by the Ca(2+)-activated Cl(-) channels, anoctamin-1 and CLCA4, as immunohistochemical labeling did not reveal protein expression within muscle or pacemaker cell networks. In summary, these results suggest that spontaneous uterine contractions may be generated by a Kit-negative pacemaker cell type or uterine myocytes, likely involving the activity of a yet-unidentified Cl(-) channel.

show abstract

Section: -Conductances and Uterine Pacemaker Eventsmentioning

confidence: 90%

Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade1

Dodds

Staikopoulos

Beckett

2015

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…Mechanisms of Cl − ‐dependent secretion in epithelia are outside the scope of this brief review (for detailed coverage see excellent recent reviews by Jang & Oh, 2014 and Pedemonte & Galietta, 2014). It is worth mentioning though that ANO1‐mediated CaCCs in epithelia are also coupled to G q/11 –GPCR–PLC–IP 3 pathways, highlighting once again a functional link between ANO1 and the ER.…”

Section: Activation Of Ano‐mediated Caccs By Localized Ca2+ Signals Imentioning

confidence: 99%

“…Thus, the G q/11 receptor ligands ATP, substance P, acetylcholine, endothelin 1, angiotensin II and histamine have all been shown to activate CaCCs in epithelial cells of various types by inducing ER Ca 2+ release (Hartzell et al . 2005; Jang & Oh, 2014; Pedemonte & Galietta, 2014). …”

Section: Activation Of Ano‐mediated Caccs By Localized Ca2+ Signals Imentioning

confidence: 99%

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Jin

Shah

et al. 2014

The Journal of Physiology

View full text Add to dashboard Cite

Ca2+‐activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin‐1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca2+ sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca2+ for activation. However, global Ca2+ levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca2+ transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co‐localize with sources of intracellular Ca2+ signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca2+ release sites of the intracellular Ca2+ stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

show abstract

“…ANO1 is known to mediate various physiological functions, such as fluid and electrolyte secretion, gut motility, vascular smooth muscle contraction, and thermal nociception (14).…”

mentioning

confidence: 99%

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

Young

Wee

Jung

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca 2+ -activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHTdependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.enign prostatic hyperplasia (BPH) is characterized by the anatomical enlargement of the prostate gland and is one of the most common diseases among elderly men (1). More than 50% of men aged more than 60 suffer from lower urinary tract symptoms, including urinary hesitancy, weak stream, and nocturia, which are commonly caused by bladder obstruction (2). The availability of testosterone or dihydrotestosterone (DHT) is known to cause the development of histologically characterized BPH (3). Clinical reports on BPH have suggested a positive association between BPH and prostate cancer, with increased risk of and mortality from prostate cancer among BPH patients (4). However, some epidemiologic studies have reported that BPH is not a cause of prostate cancer (5). Despite the controversy on the association between prostate cancer and BPH, common risk factors for the two diseases include chronic inflammation, metabolic disturbance, and genetic variation (6, 7). Regardless of its association with prostate cancer, BPH is still a social issue for the elderly, but the etiologic mechanisms of its pathology remain unknown. Anoctamin1 (ANO1, also known as TMEM16A) encodes a Ca 2+ -activated chloride channel (CaCC) (8-10), and is widely expressed in secretory epithelia, including the salivary gland, trachea (11), and intestine, smooth muscle (12), and sensory neurons (13). ANO1 is known to mediate various physiological functions, such as fluid and electrolyte secretion, gut motility, vascular smooth muscle contraction, and thermal nociception (14).ANO1 has been suggested to be a regulator of cell proliferation and tumorigenesis, even before it was discovered as a CaCC, and is highly expressed in several carcinomas, including gastrointestinal stromal tumors (15), esophageal squamous cell carcinoma (16), head and neck squamous cell carcinoma (17), oral cancer (18), breast cancer (19), and prostate cancer (20). The disruption of Ano1 or the administration of a pharmacological ANO1 inhibitor impairs the proliferation of interstitial cells of Ca...

show abstract

Anoctamin 1 in secretory epithelia

Cited by 44 publications

References 65 publications

Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade1

Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade1

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

Contact Info

Product

Resources

About

Anoctamin 1 in secretory epithelia

Cited by 44 publications

References 65 publications

Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade1

Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade1

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

Contact Info

Product

Resources

About

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals