| dc.contributor.author | Shi, Chanjuan. | en_US |
| dc.date.accessioned | 2014-10-21T12:37:21Z | |
| dc.date.available | 2002 | |
| dc.date.issued | 2002 | en_US |
| dc.identifier.other | AAINQ75723 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55875 | |
| dc.description | Non-pigmented ciliary epithelial (NPCE) cells take part in the secretion of aqueous humor in the eye. In this study, cell swelling- and G protein-coupled receptor (GPCR)-associated signaling pathways that regulate CI channels in SV40-transformed mammalian NPCE cells were examined. | en_US |
| dc.description | In rabbit NPCE cells, hyposmotic stimulation leading to cell swelling activated an outwardly rectifying volume-sensitive Cl- current (ICl,vol) regulated by Ca2+ and phosphorylation. Noise analysis revealed that swelling activated a high density of Cl channels with a conductance <1 pS. Further investigation demonstrated that a protein tyrosine kinase/phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein phosphatase signaling cascade participates in activation of ICl,vol in rabbit NPCE cells. In contrast, increases in protein kinase C (PKC) activity inhibited ICl,vol ClC-3 Cl channel mRNA was detected, and an anti-ClC-3 antibody and antisense ClC-3 oligonucleotides inhibited ICl,vol suggesting the contribution of ClC-3 channels to ICl,vol. | en_US |
| dc.description | In human NPCE cells, A3 adenosine and CB1 receptors coupled to PTX-sensitive Gi proteins activated a PKC-sensitive Cl- current. A3 and CB1 receptor activation of the Cl- current involved GE9-mediated signaling pathways, and was independent of PI3K activity. Endogenous CB1 receptor mRNA expression was detected in SV40-transformed human NPCE cells, and transfection with human CB1 receptors enhanced the endogenous CB1 receptor-activated Cl- current, consistent with increased receptor protein. A CB1 receptor inverse agonist SR 141716 had on effect on basal Cl-, indicating low constitutive receptor activity in transfected cells. However, SR 141716 decreased the A3 receptor-activated Cl- current, suggesting an interaction between CB1 and A3 receptors. | en_US |
| dc.description | Taken together, these studies provide evidence that Cl channels in NPCE cells are regulated by cell swelling- and GPCR-coupled signaling pathways. As Cl channels in NPCE cells are rate-limiting for aqueous humor secretion, alterations in Cl channel activity should alter aqueous humor secretion and intraocular pressure. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2002. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.title | Regulation of chloride channels in non-pigmented ciliary epithelial cells in the mammalian eye. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
