Effects of timolol, terbutaline and forskolin on IOP, aqueous humour formation and ciliary cyclic AMP levels in the bovine Eye

Mohammad Shahidullah, William S. Wilson, John Cameron Millar

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We have studied the effects of terbutaline, timolol, forskolin and 8-bromo cyclic AMP on aqueous humour formation, intraocular pressure and on ciliary epithelial cyclic AMP levels, either in presence or in absence of IBMX, using the bovine isolated arterially perfused eye, excised ciliary processes and cultured ciliary epithelium. Both terbutaline, a βadrenoceptor agonist, and timolol, a βadrenoceptor antagonist, caused significant reduction in aqueous humour formation and intraocular pressure but produced no effect on ciliary epithelial cyclic AMP content in the absence of IBMX. Even a three times higher dose of terbutaline was entirely ineffective in producing any effect on ciliary cyclic AMP in the perfused eye. On the other hand, terbutaline at the IOP-reducing dose, produced a significant increase in cyclic AMP when injected after 30 min perfusion with IBMX. Incubation of excised ciliary processes or cultured ciliary epithelial cells with terbutaline (10-6 to 10-4 M) produced concentration-dependent increases in cyclic AMP, in both tissues, even in the absence of IBMX. Forskolin, which stimulates cyclic AMP synthesis without interacting with cell surface receptors, was found to produce highly significant increases in ciliary cyclic AMP content both in presence and in absence of IBMX but had no effect on aqueous humour formation in the isolated eye. IBMX perfused at concentrations of 1 mM or 10 μM had no effect on basal levels of ciliary cyclic AMP but the 1 mM concentration produced a marked and significant reduction in IOP. Direct application of 8-bromo cyclic AMP, a cell permeable analogue, more resistant to hydrolysis by phosphodiesterases, had also no effect on aqueous humour formation in the perfused eye. It is concluded that in the bovine arterially perfused eye, the correlation between the aqueous humour formation rate and ciliary epithelial cyclic AMP content is unclear.

Original languageEnglish
Pages (from-to)519-528
Number of pages10
JournalCurrent Eye Research
Volume14
Issue number7
DOIs
StatePublished - 1 Jan 1995

Fingerprint

Terbutaline
Timolol
Aqueous Humor
Colforsin
Cyclic AMP
1-Methyl-3-isobutylxanthine
8-Bromo Cyclic Adenosine Monophosphate
Intraocular Pressure
Adrenergic Receptors
Phosphoric Diester Hydrolases
Cell Surface Receptors
Hydrolysis
Epithelium
Perfusion
Epithelial Cells

Keywords

  • Aqueous humour
  • Cell culture
  • Ciliary epithelium
  • Cyclic AMP
  • IOP

Cite this

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abstract = "We have studied the effects of terbutaline, timolol, forskolin and 8-bromo cyclic AMP on aqueous humour formation, intraocular pressure and on ciliary epithelial cyclic AMP levels, either in presence or in absence of IBMX, using the bovine isolated arterially perfused eye, excised ciliary processes and cultured ciliary epithelium. Both terbutaline, a βadrenoceptor agonist, and timolol, a βadrenoceptor antagonist, caused significant reduction in aqueous humour formation and intraocular pressure but produced no effect on ciliary epithelial cyclic AMP content in the absence of IBMX. Even a three times higher dose of terbutaline was entirely ineffective in producing any effect on ciliary cyclic AMP in the perfused eye. On the other hand, terbutaline at the IOP-reducing dose, produced a significant increase in cyclic AMP when injected after 30 min perfusion with IBMX. Incubation of excised ciliary processes or cultured ciliary epithelial cells with terbutaline (10-6 to 10-4 M) produced concentration-dependent increases in cyclic AMP, in both tissues, even in the absence of IBMX. Forskolin, which stimulates cyclic AMP synthesis without interacting with cell surface receptors, was found to produce highly significant increases in ciliary cyclic AMP content both in presence and in absence of IBMX but had no effect on aqueous humour formation in the isolated eye. IBMX perfused at concentrations of 1 mM or 10 μM had no effect on basal levels of ciliary cyclic AMP but the 1 mM concentration produced a marked and significant reduction in IOP. Direct application of 8-bromo cyclic AMP, a cell permeable analogue, more resistant to hydrolysis by phosphodiesterases, had also no effect on aqueous humour formation in the perfused eye. It is concluded that in the bovine arterially perfused eye, the correlation between the aqueous humour formation rate and ciliary epithelial cyclic AMP content is unclear.",
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Effects of timolol, terbutaline and forskolin on IOP, aqueous humour formation and ciliary cyclic AMP levels in the bovine Eye. / Shahidullah, Mohammad; Wilson, William S.; Millar, John Cameron.

In: Current Eye Research, Vol. 14, No. 7, 01.01.1995, p. 519-528.

Research output: Contribution to journalArticle

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