Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells.

Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Research Abstract Details 

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Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Abstract Text:

Vidhya R Rao,Raghu R Krishnamoorthy,Thomas Yorio,

Primary open angle glaucoma (POAG) is a progressive optic neuropathy, characterized, in part by extensive extra cellular matrix remodeling and collapse of the lamina cribrosa (LC). Endothelin-1 (ET-1), a potent vasoactive peptide and its receptors, endothelin receptor A (ET(A)) and endothelin receptor B (ET(B)), have been implicated in glaucomatous optic neuropathy. In this study we examined the expression of ET-1 and its receptors in GFAP negative LC cells. RT-PCR analysis revealed that LC cells express both ET(A), ET(B) receptors and prepro- ET-1, the primary gene transcript of ET-1. A dose-dependent increase in intra-cellular calcium concentrations was observed in the presence of 1, 10 and 100nM ET-1. Increased intracellular calcium concentrations were blocked by the ET(A) selective antagonist BQ610 but not by the ET(B) specific antagonist BQ788. Desensitization to ET(A)-mediated increase in intracellular calcium was observed in LC cells following pre-treatment with ET-1 for 24h. Western blot analysis of LC cells treated with ET-1 for 24h revealed a decreased expression of ET(A) receptor protein at 1, 10 and 100nM concentrations, while a dose dependent increase in the ET(B) receptor was observed with a significant increase at 100nM. Quantitative PCR showed a dose-dependent decrease in ET(A) receptor mRNA levels and an increase in the mRNA levels of ET(B) receptors. A Griess colorimetric assay was used to measure the NO released from LC cells and ET-1 induced a dose-dependent increase in NO release which was significant at 100nM concentration. ET-1 induced NO release was significantly blocked by BQ788, an ET(B) selective antagonist, and as well as BQ610, an ET(A) selective antagonist. These results suggested that human lamina cribrosa cells expressed functional ET(A) and ET(B) receptors and their expression and function was altered in response to prolong exposure to ET-1. This may have an implication in the normal physiology of LC cells and in POAG subjects where elevated levels of ET-1 could impact LC function.

Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Publishing Authors By Initials

VR Rao,RR Krishnamoorthy,T Yorio,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Experimental eye research

VOLUME: 84

Page Numbers: 1115-24

Journal Abbreviation: Exp. Eye Res.

ISSN: 0014-4835

DAY: 22

MONTH: 02

YEAR: 2007

Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Information

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LANGUAGE: eng

NlmUniqueID: 370707

Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells. Information

Substance Name: Calcium

Registry Number: 7440-70-2

Grant and Affiliation Information for Endothelin-1, endothelin A and B receptor expression and their pharmacological properties in GFAP negative human lamina cribrosa cells.

AFFILIATION: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.

Country: England

AGENCY: United States NEI

GRANT: EY11979

ACRONYM: EY

MEDLINETA: Exp Eye Res

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