ML-7, Chelerythrine and Phorbol Ester Increase Outflow Facility in the Monkey Eye

Tian, Baohe; Brumback, Lyndia C.; Kaufman, Paul L.

doi:10.1006/exer.2000.0919

Cited by 39 publications

(24 citation statements)

References 45 publications

(44 reference statements)

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“…Since the vascular anatomy of the out¯ow pathways and orbit in rabbit differs from that of the primates (Poyer et al, 1992), there is also an alternative that the signi®cant IOP-lowering effect of ML-9 in rabbit eyes may be related to changes in the permeability of vasculature in the anterior chamber. However, Tian et al (2000a) have reported that ML-7, another MLCK inhibitor, increased the out¯ow facility in primates. The data of the two MLCK inhibitors support the notion that inhibition of MLCK seems to target the conventional out¯ow to a large extent.…”

Section: Discussionmentioning

confidence: 96%

A Myosin Light Chain Kinase Inhibitor, ML-9, Lowers the Intraocular Pressure in Rabbit Eyes

Honjo

Inatani

Kido

et al. 2002

Experimental Eye Research

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Section: Discussionmentioning

confidence: 96%

A Myosin Light Chain Kinase Inhibitor, ML-9, Lowers the Intraocular Pressure in Rabbit Eyes

Honjo

Inatani

Kido

et al. 2002

Experimental Eye Research

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“…They reported that the candidates show cytoskeletal-modulating efficacy in vitro and reduce IOP in vivo. [18][19][20] These findings may suggest the possibility that ECA derivatives, especially SA9000, will show ocular hypotensive effect because of their potent cytoskeletal modulating efficacy of trabecular meshwork cells.…”

Section: Resultsmentioning

confidence: 99%

New Ethacrynic Acid Derivatives as Potent Cytoskeletal Modulators in Trabecular Meshwork Cells

Shimazaki

Suhara

Ichikawa

et al. 2004

Biological & Pharmaceutical Bulletin

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“…In control (vehicle-treated) animals, the vehicle (saline) was applied topically to both eyes, and the sampling schedule was the same as those of the treatment group. The topical pretreatment with antagonists norbinaltorphimine (norBNI, 100 g/25 l; Tocris Cookson Inc., Ballwin, MO) or chelerythrine chloride (10 g/25 l; Sigma-Aldrich), a PKC inhibitor, preceded the challenge with BRE by 0.5 h. The topical doses of antagonists were determined from previous experimentation in rabbits (Russell et al, 2000) or were extrapolated from previously published in vivo doses in rabbits (Sandhu et al, 1997) and monkeys (Tian et al, 2000).…”

Section: Methodsmentioning

confidence: 99%

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

Potter¹,

Russell²,

Manhiani³

2004

J Pharmacol Exp Ther

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A relatively selective agonist of opioid receptors (KOR), bremazocine (BRE), lowers intraocular pressure in rabbits, in part, by increasing natriuretic peptide levels in aqueous humor and by enhancing total outflow facility (TOF). Natriuretic peptide (NP) levels [atrial NP (ANP), brain NP (BNP), and C-type NP (CNP)] were measured in aqueous humor of rabbits either by radioimmunoassay or enzyme immunoassay. TOF was determined in rabbits by two-level constant pressure perfusion of the anterior chamber. Experimental regimens included topical treatment with BRE in the presence or absence of KOR antagonist (norbinaltorphimine), protein kinase C inhibitor (chelerythrine), and natriuretic peptide receptor antagonist (isatin). The rank order of basal NP levels in aqueous humor of rabbits was BNP & CNP Ͼ ANP. Topical administration of BRE (1-100 g) caused dose-related elevations of CNP levels in aqueous humor that were inhibited by topical pretreatment with either norbinaltorphimine (100 g, bilaterally) or chelerythrine (10 g, bilaterally). Topically administered BRE (100 g) also elevated levels of ANP and BNP in aqueous humor and evoked an 80% increase in TOF. The increase in TOF was antagonized by topical pretreatment with either norbinaltorphimine (100 g, bilaterally) or isatin (100 g, bilaterally). Bremazocine induced an increase in NP (ANP, BNP, and CNP) levels and TOF in rabbits by activating KOR. The increase in CNP levels elicited by BRE was inhibited by norbinaltorphimine and chelerythrine; therefore, this event is most likely mediated by a KOR-linked activation of protein kinase C. These data provide evidence that the increase in TOF elicited by BRE was mediated by a KORactivated paracrine effect of NPs on tissues within ocular outflow tract(s).Neuroendocrine regulation of fluid homeostasis throughout the body depends, in part, on the activity of the natriuretic peptide system. Of the three natriuretic peptides [i.e., atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)], the sequences of ANP and CNP are more highly conserved among the species, whereas the structure of BNP varies greatly. It has been proposed that natriuretic peptides generated within the eye contribute to the regulation of aqueous humor dynamics; however, the understanding of how this ocular neuroendocrine system is modulated is very limited.Recently, molecular evidence has been presented for neuroendocrine functions in the ciliary epithelium Ortego and Coca-Prados, 1999). Moreover, it has been postulated that natriuretic peptides released by drugs from ciliary epithelial cells could then act in an autocrine and/or paracrine manner to change intraocular pressure (IOP). Recent reports have shown that ocular hypotensive drugs such as opioid receptor (KOR) agonists (bremazocine) (Russell et al., 2001;Russell and Potter, 2002) and imidazoline-1/␣2 agonists (Ogidigben et al., 1999(Ogidigben et al., , 2002 elevate ANP levels in aqueous humor of rabbits.The current study was conducted to: 1) ...

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ML-7, Chelerythrine and Phorbol Ester Increase Outflow Facility in the Monkey Eye

Cited by 39 publications

References 45 publications

A Myosin Light Chain Kinase Inhibitor, ML-9, Lowers the Intraocular Pressure in Rabbit Eyes

A Myosin Light Chain Kinase Inhibitor, ML-9, Lowers the Intraocular Pressure in Rabbit Eyes

New Ethacrynic Acid Derivatives as Potent Cytoskeletal Modulators in Trabecular Meshwork Cells

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

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