Adrenergic Drug Effects on Cyclic AMP in Cultured Human Trabecular Meshwork Cells

Friedman, Zvi; Bloom, Ernest; Polansky, JonR.

doi:10.1159/000055513

Cited by 5 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These early studies showed that both timolol (1 mM) and racemic betaxolol (1 mM) inhibited epinephrine-induced cAMP production. Our studies compare favorably with recent published reports showing K i values of 0.8 nM for timolol, and 2 nM for ICI-118551 (21) in cultured primary human TM cells. Interestingly, racemic betaxolol was weaker in these studies (K i 5 850 nM) when compared to our results (K i 5 19 nM).…”

Section: Discussionsupporting

confidence: 91%

“…yielded a range of potencies (EC 50 values) from 66 6 8 nM for isoproterenol to .10,000 nM for phenylephrine. Our cell growth conditions may have produced a higher receptor density or more efficient coupling to adenylyl cyclase thus allowing for an increased amount of cAMP production and greater sensitivity in the assays than previous studies (12,21). Experiments conducted with cultured primary human ciliary epithelial cells produced a stimulation of cAMP production of 1.4 fold for norepinephrine (1 mM), 2.5 fold for epinephrine (1 mM), and 3.5 fold for isoproterenol (1 mM) above basal values (12).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Adenylyl Cyclase Activity Mediated by β-Adrenoceptors in Immortalized Human Trabecular Meshwork and Non-Pigmented Ciliary Epithelial Cells

Crider

Sharif

2002

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Non-pigmented ciliary epithelial (NPE) and trabecular meshwork (TM) cells are important in maintaining normal aqueous humor dynamics through the inflow and outflow routes, respectively. The current studies were undertaken to evaluate the ability of several beta-adrenergic receptor agonists to stimulate various antagonists to inhibit cAMP production in cultured immortalized human TM and NPE cells using an automated enzyme immunoassay. Isoproterenol was the most potent agonist in both the NPE and TM cells. The rank order of potency of agonists in NPE and TM cells, respectively, was: isoproterenol [EC50 = 37 and 66 nM] > epinephrine [EC50 = 112 and 526 nM] > albuterol [EC50 = 426 and 785 nM] > norepinephrine [EC50 = 3 and > 10 microM] > phenylephrine [EC50 > 10 microM for both] = dopamine [EC50 > 10 microM for both](n = 3-19). The isoproterenol-induced cAMP production was inhibited by various antagonists with the following rank order of potency in NPE and TM cells, respectively: propranolol [Ki = 0.2 and 0.3 nM] = ICI-118551 [Ki = 0.5 and 0.4 nM] > levobunolol [Ki = 1.1 and 2.1 nM] > levobetaxolol [Ki = 13 and 14 nM] = racemic betaxolol [Ki = 43 and 19 nM] > dextrobetaxolol [Ki = 2,705 and 1,980 nM] > atenolol [Ki > 4,000 nM for both] (n = 3-7). These detailed pharmacological studies using a variety of agonists and antagonists further supported the presence of beta2-adrenergic receptors in immortalized human NPE and TM cells.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Adenylyl Cyclase Activity Mediated by β-Adrenoceptors in Immortalized Human Trabecular Meshwork and Non-Pigmented Ciliary Epithelial Cells

Crider

Sharif

2002

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

show abstract

“…[10][11][12] Long-term use of timolol causes functional and morphological ef-fects on trabecular meshwork cells. [13][14][15][16] Although the clinical effects of timolol on IOP reduction are well established, little is known about the potential effects of timolol on expression of glaucoma genes. If induction of glaucoma genes has the potential to affect disease pathologic features, then it is important to know whether glaucoma medications used to treat patients can affect expression levels of glaucoma gene transcripts or products in relevant tissue types.…”

mentioning

confidence: 99%

Effects of Timolol on MYOC, OPTN, and WDR36 RNA Levels

et al. 2008

View full text Add to dashboard Cite

To evaluate if timolol affects expression of 3 open-angle glaucoma genes and to study its ability to modulate dexamethasone-induced up-regulation of MYOC. Methods: We used quantitative polymerase chain reaction assay of glaucoma gene transcript levels from human trabecular meshwork (HTM) cultures exposed to 3 different doses of timolol. Three HTM cell cultures were grown with or without 1 of 3 timolol doses in the presence or absence of dexamethasone. Results: All 3 concentrations of timolol reduced MYOC RNA levels in 1 HTM culture compared with an untreated control and showed negligible effects in the other 2 cultures. Timolol had no effect on dexamethasone-induced MYOC transcript levels in any of the 3 cultures. Timolol, dexamethasone, and dexamethasone plus timolol had a negligible effect on OPTN and WDR36 RNA levels. Conclusions: Timolol can reduce MYOC RNA levels in HTM cultures from some individuals. Timolol does not alter OPTN or WDR36 levels or ameliorate MYOC induction by dexamethasone in vitro. Clinical Relevance: It remains to be determined whether timolol could reduce production of misfolded myocilin protein by HTM cells in individuals with MYOC missense mutations. A broader survey of interindividual variation in response to timolol as well as mechanistic studies are still needed before potential therapeutic implications can be explored.

show abstract

Cell volume response to hyposmotic shock and elevated cAMP in bovine trabecular meshwork cells

Srinivas

Maertens

Goon

et al. 2004

Experimental Eye Research

View full text Add to dashboard Cite

Adrenergic Drug Effects on Cyclic AMP in Cultured Human Trabecular Meshwork Cells

Cited by 5 publications

References 16 publications

Adenylyl Cyclase Activity Mediated by β-Adrenoceptors in Immortalized Human Trabecular Meshwork and Non-Pigmented Ciliary Epithelial Cells

Adenylyl Cyclase Activity Mediated by β-Adrenoceptors in Immortalized Human Trabecular Meshwork and Non-Pigmented Ciliary Epithelial Cells

Effects of Timolol on MYOC, OPTN, and WDR36 RNA Levels

Cell volume response to hyposmotic shock and elevated cAMP in bovine trabecular meshwork cells

Contact Info

Product

Resources

About