Pharmacological and Functional Characterization of Endothelin Receptors in Bovine Trabecular Meshwork and Ciliary Muscle

Choritz, Lars; Rosenthal, Rita; Fromm, Michael; Foerster, Michael; Thieme, Hagen

doi:10.1159/000086471

Cited by 20 publications

(17 citation statements)

References 54 publications

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“…ET-1 Ca 2+ -independent contraction seems to be mediated both by ET-AR and ET-BR, since specific inhibitors for each receptor lead to decreased responses but not to a complete abolishment of TM contractility. Choritz et al reported almost no alteration in ET-1-induced BTM contraction after incubation with the ET-BR specific antagonist BQ788, suggesting that this receptor should not contribute to ET-1 contraction of BTM in the presence of Ca 2+ [17]. In a condition of Ca 2+ -depletion, even if ET-AR inhibition had a greater effect on BTM contractility, we were able to demonstrate an ET-1-induced contraction mediated by ET-BR.…”

Section: Discussionsupporting

confidence: 42%

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Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork

Renieri

Choritz

Rosenthal

et al. 2008

Graefes Arch Clin Exp Ophthalmol

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Section: Discussionsupporting

confidence: 42%

“…Both ET receptors ET-AR and ET-BR have been shown to occur in this tissue in bovine and human studies [16][17][18]. ET-receptors are also expressed in ciliary muscle, and both bovine CM and TM contract when exposed to ET-1 (for a review, see [4]).…”

Section: Discussionmentioning

confidence: 99%

Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork

Renieri

Choritz

Rosenthal

et al. 2008

Graefes Arch Clin Exp Ophthalmol

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“…EG-1 is capable of causing contraction of TM and, thus, a decrease in the intertrabecular space with an increase in the resistance of the intraocular fluid outflow. EG-1 also causes contraction of the ciliary muscle and tension on the TM [22]. Since the elucidation that TM and ciliary body express both receptor subtypes for ET-1 and that EG-1 is present in the intraocular fluid, it has been suggested that ET-1 has influence on the IOP by affecting the balance between the functionally antagonistic contractile forces of these tissues.…”

Section: Introductionmentioning

confidence: 99%

“…A mechanism of control on IOP has also been considered, namely inhibition of the Na + /K + -ATPase in the non-pigmented ciliary epithelial cells in cultures. In vivo this could mean decreased production of intraocular fluid and, hence, a decrease of IOP [22].…”

Section: Introductionmentioning

confidence: 99%

Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma

Mihaylova

Petkova

Rankova-Yotova

et al. 2017

Biotechnology & Biotechnological Equipment

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Endothelin-1 (ET-1) is a potent vasoconstrictor and is considered to have a key role in the regulation of ocular perfusion and glaucoma pathogenesis. High ET-1 and ET A -receptor levels are reported in patients with primary open-angle glaucoma (POAG). We compared the mean plasma ET-1 and ET Areceptor concentration of controls and patients with early and advanced POAG stage, and assessed the correlation with the retinal nerve fibre layer (RNFL) thickness. The study included a total of 75 participants, aged 45-83 years: 25 (controls), 22 (early glaucoma) and 28 (advanced glaucoma). The plasma concentration of ET-1 and ET A -receptor was determined by enzyme-linked immunosorbent assay. The RNFL thickness was evaluated with spectral-domain optical coherence tomography. The mean ET-1 concentration was lower in the control group (4.88 § 1.75 pg/mL) than in the early and advanced POAG group (6.33 § 2.38 and 6.34 § 1.56 pg/mL). Statistically significant difference was found between the mean ET-1 concentrations in controls and glaucoma patients (p = 0.029 -early glaucoma, p = 0.018 -advanced glaucoma), and no significant difference was observed between the two POAG groups (p = 0.998). The mean ET A -receptor concentration was highest in the control group (1209.28 § 314.48 pg/mL) and the differences between the three groups were significant. Significant relationship was found only between ET-1 and RNFL. This study demonstrated the role of ET-1 in glaucoma pathogenesis based on the observed significant high ET-1 and ET A -receptor plasma levels in POAG patients. A new therapeutical approach needs to be considered in some patients.

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“…The following ET-1-induced contraction in the presence of BQ-123 was strongly reduced, whereas BQ-788 has no effect. (B) Expression of endothelin receptors verified with Western blot analysis in cultured cells of bovine and human trabecular meshwork (modified from Choritz et al, 2005;Copyright S. Karger AG, Basel;Rosenthal et al, 2007).…”

Section: Figurementioning

confidence: 99%

Endothelin antagonism as an active principle for glaucoma therapy

Rosenthal

Fromm

2011

British J Pharmacology

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Endothelin, the most potent vasoactive peptide known to date, has been suggested to play a potential role in the pathogenesis of open-angle glaucoma. Open-angle glaucoma is the most common optic nerve head neuropathy and is associated with a loss of retinal ganglion cells and visual field damage. Although an increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, other factors such as a reduced ocular blood flow play an important role for appearance of the disease. Thus, treatment of glaucoma is focused on lowering of intraocular pressure and preventing the occurrence or progression of glaucomatous optic neuropathy. Endothelin participates in the regulation of intraocular pressure by an effect on trabecular outflow, the main route for aqueous humour outflow from the eye. Trabecular outflow is modulated by trabecular meshwork contractility which is affected by endothelin. In addition to the effects of endothelin in the anterior part of the eye, the vasoconstrictor causes a decrease in ocular blood flow followed by pathological changes in the retina and the optic nerve head which is assumed to contribute to the degeneration of retinal ganglion cells. In sum, inhibition of endothelin signalling leads to lowering of intraocular pressure and exerts neuroprotective effects. Thus, endothelin antagonism in the eye represents a promising approach for pharmacological treatment of glaucoma. AbbreviationsECE, endothelin-converting enzyme; ET-1, endothelin-1; ETA receptor, endothelin receptor A; ETB receptor, endothelin receptor B; FP receptor, prostaglandin F receptor; IOP, intraocular pressure; MLCK, myosin light chain kinase; MMP, matrix-metalloproteinase; OBF, ocular blood flow; PG, prostaglandin; ROCK, Rho kinase; RGC, retinal ganglion cell IntroductionEndothelin-1 (ET-1), the most potent vasoconstrictor known to date, is expressed in many organs and tissues and has been shown to play an important role in vascular homeostasis (Yanagisawa et al., 1988) as well as in a variety of pathological processes (Levin, 1995).In the human eye endothelin is detectable in the posterior part, especially in the choroid, retinal blood vessels, retinal pigment epithelium and optic nerve (Wollensak et al., 1998;Narayan et al., 2004). The precise source of endothelin in the posterior segment of the eye remains unclear. One possible source is the retinal pigment epithelium, which secretes ET-1 towards the basolateral side, suggesting an involvement in the regulation of choroidal blood flow (Narayan et al., , 2004Dibas et al., 2005a). The ET-1 synthesis and release from optic nerve head astrocytes as seen in cultured human cells may contribute to the signal in the optic nerve (Desai et al., 2004).In the anterior part of the eye, ET-1 was found in the iris, non-pigmented ciliary epithelium, ciliary muscle, as well as in the trabecular meshwork, endothelial cells lining Schlemm's canal and corneal epithelium (Wollensak et al., 1998;Fernandez-Durango et al., 2003). Apart from its localization in ocular tissues, ...

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Pharmacological and Functional Characterization of Endothelin Receptors in Bovine Trabecular Meshwork and Ciliary Muscle

Cited by 20 publications

References 54 publications

Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork

Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork

Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma

Endothelin antagonism as an active principle for glaucoma therapy

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