Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0595921 (intraocular pressure)
 11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Direct administration of cyclic-AMP into the anterior chamber increases the outflow facility of the eye for aqueous humor. This is consistent with the hypothesis that catecholamines lower the intraocular pressure of the rabbit eye, at least in part, by a cyclic-AMP-mediated mechanism. This mechanism is active in the outflow channels and increases the rate at which aqueous humor leaves the anterior chamber.
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PMID:Adenosine 3',5'-monophosphate increases the outflow of aqueous humor from the rabbit eye. 16 98

Our previous studies showed that cyclic-AMP increases the outflow facility of the eye of the rabbit. In this investigation, an analogue of cyclic-AMP, the 8-methylthio derivative, perfused into the anterior chamber of the eye of the vervet monkey, increased outflow facility twofold. This observation supports the hypothesis that cyclic-AMP mediates the action of adrenergic agents to reduce intraocular pressure in the primate eye.
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PMID:Adenosine 3',5'-monophosphate analogue increases the outflow facility of the primate eye. 16 6

The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated.
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PMID:Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. 19 83

Timolol, which binds to beta-adrenergic receptors, is a potent antagonist of the catecholamine-stimulated synthesis of cyclic AMP. However, the actual mechanism of action by which timolol reduces intraocular pressure is not readily apparent. Compared to its efficacy in human eyes, the drug is relatively ineffective in rabbit eyes. A reasonable postulate is that soon after administration, timolol blocks endogenous adrenergic stimulation contributing to the formation of aqueous humor by the ciliary processes. Nevertheless, the long-lasting reduction of intraocular pressure persists at a time when the drug is no longer bound to beta-adrenergic receptors.
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PMID:Experimental studies on the mechanism of action of timolol. 22 48

In order to elucidate the influence of acute ocular inflammation on the aqueous humor dynamics and intraocular pressure (IOP), we carried out argon laser photo-coagulations on the rabbit irises and determined the concentrations of aqueous humor prostaglandins (PGs), cyclic AMP and protein. The IOP changed in a biphasic manner, i.e. initial hypertension and later hypotension. The concentrations of aqueous humor PG E2, PG F2 alpha and protein increased markedly after laser irradiation and then decreased gradually, although the concentrations of PG E2 and protein remained significantly higher than the baseline values at 24 hours after the irradiations. The concentrations of aqueous cyclic AMP of the irradiated eyes and control eyes were 67.8 pmol/ml and 29.3 pmol/ml, respectively. We presumed that the increase in concentration of aqueous cyclic AMP and breakdown of the blood-aqueous barrier by PGs caused the reactive hypotension.
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PMID:[Effects of argon laser irradiation of the iris on the concentration of aqueous prostaglandins and cyclic AMP]. 131 34

We have examined the effect of venom sac extract (VSE), prepared from two hymenopteran species, on intracellular cyclic AMP (cAMP) accumulation in a cultured human cell line. VSE prepared from the oriental hornet (Vespa orientalis) and from the paper wasp (Polistes carolina) induced an increase in accumulation of cAMP in human, transformed, non-pigmented, ciliary epithelial cells. The effect of V. orientalis VSE on intracellular cAMP was dose-dependent. Blocking the response of adenylate cyclase-linked beta-adrenergic receptors was without effect on this cellular response to VSE. On the other hand, the response to VSE prepared from both species was suppressed almost totally by the H2-histamine receptor-specific antagonist, cimetidine. The findings are discussed in the light of earlier observations that described a significant reduction in intraocular pressure in vertebrate animals treated with V. orientalis VSE.
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PMID:Hymenopteran venom stimulates adenylate cyclase in cultured human cells through a histamine receptor. 131 17

1. Calcitonin gene-related peptide (CGRP) is involved in ocular neurogenic inflammation in the rabbit, causing vasodilatation in the anterior uvea, breakdown of the blood-aqueous barrier, increase in the intraocular pressure (IOP) and rise in the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content in the aqueous humour. So far there is no means of preventing these CGRP-induced ocular effects. 2. In the present study, the effect of intravenous methysergide (1-10 mg kg-1, b.w.) on CGRP-induced changes in the IOP, blood-aqueous barrier and cyclic AMP content in the aqueous humour was studied in vivo. The effect of methysergide on CGRP-induced vasodilatation both in vivo and in vitro was also investigated. 3. Methysergide decreased intraocular pressure but had only a transient effect on blood pressure. Methysergide decreased the regional blood flow in ocular tissues by 53-65%, but did not have such a vasoconstrictor effect in most extra-ocular tissues studied. 4. Methysergide inhibited CGRP-induced vasodilatation, increase in the IOP, breakdown of the blood-aqueous barrier and increase in the cyclic AMP content in the aqueous humour in vivo. 5. In vitro, methysergide alone did not have effects on the vascular tone in isolated ophthalmic artery of rabbit. However, it potentiated noradrenaline (NA)-induced contraction. There were no differences in the IC50 values for CGRP on the NA-induced contraction in the presence and absence of methysergide, indicating that methysergide has no direct effect on the vasorelaxant effect of CGRP in vitro. 6. The present study demonstrates that in the rabbit eye methysergide inhibits CGRP-induced changes.One inhibitory mechanism of methysergide may be to enhance the effect of a vasoconstrictor (NA) to antagonize the vasodilator effect of CGRP. The present findings suggest that a methysergide-sensitive mechanism may be used to limit some pathophysiological conditions in the eye that involve neurogenic inflammation and the release of CGRP.
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PMID:Inhibitory effect of methysergide on calcitonin gene-related peptide-induced vasodilatation and ocular irritative changes in the rabbit. 132 81

Rabbits have circadian rhythms of intraocular pressure (IOP) and aqueous flow. The dark phase increases of IOP and flow are associated with increased aqueous cyclic AMP. If the daily rhythm of aqueous cyclic AMP reflects changes of tissue levels of cyclic AMP which mediate one of the mechanisms which control the rhythms of IOP and aqueous flow, then it must be a circadian rhythm as are the rhythms of IOP and flow. A recent report showed no change in aqueous cyclic AMP from 2 hrs before to 2 hrs after the beginning of subjective dark in animals housed in constant dark. Because the increase of intraocular pressure at the same times did persist in constant dark, the authors concluded that a significant portion of the circadian rhythm of IOP is unrelated to cyclic AMP mediated ocular mechanisms. However, if an inhibitor of cyclic nucleotide phosphodiesterase is added to aqueous samples after harvesting by paracentesis, it is possible to show that most of the increase of aqueous cyclic AMP from mid-light phase to mid-dark phase persists in constant dark and is therefore likely to reflect a circadian rhythm of tissue cyclic AMP.
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PMID:Rabbits have a circadian rhythm of aqueous humor cyclic AMP. 138 40

The mechanism by which pivaloyloxymethyl (POM) ester of griseolic acid (GA), a potent cyclic AMP-phosphodiesterase inhibitor, lowers intraocular pressure (IOP) in albino rabbits was studied. The rate of aqueous flow, measured by fluorophotometry, was significantly lower in GA POM ester-treated eyes (2.36 +/- 0.24 microliters/min) than in control eyes (3.02 +/- 0.24 microliters/min). Topically applied GA POM ester did not alter tonographic outflow or uveoscleral outflow. No differences in aqueous humor protein concentrations between GA POM ester-treated and control eyes were observed. It was thought that the GA POM ester lowered the IOP by decreasing the aqueous inflow. Topical application of this compound caused no inflammatory response in the eye or changes in the blood aqueous barrier.
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PMID:Effects of a cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester of griseolic acid, on aqueous humor dynamics in rabbits. 165 74

The effects of griseolic acid (GA), a cyclic-AMP phosphodiesterase (PDE) inhibitor, and its 8'-pivaloyloxymethyl (POM) ester on intraocular pressure (IOP) in rabbits were investigated. When 50 microliters of 1 and 2% GA POM ester solutions were topically applied to one eye in normal rabbits, significant IOP decreases were detected at 2 hrs and at 1 to 5 hrs, respectively. Other than ocular hypotension, no other ocular effects were detected locally even after administration of 2% GA POM ester. A more marked reduction in IOP occurred after the intravitreal injection of the GA POM ester. IOP was also reduced when GA was used in an intravitreal injection but not when it was topically applied. The difference in permeability between GA and GA POM ester across the corneal epithelium may explain why GA failed to reduced IOP following topical administration. GA and the GA POM ester inhibited cAMP PDE in rabbit ciliary body at low concentrations, the I50 being 0.075 microM and 2.4 microM, respectively, with 0.25 microM cAMP as substrate. GA and the GA POM ester markedly increased cAMP levels in vitro in iris-ciliary body specimens. Possibly, GA POM ester or its analogues may represent a new mechanistic class of ocular hypotensive agents.
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PMID:A cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester (POM-ester) of griseolic acid, lowers rabbit intraocular pressure. 166 21


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