Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency

Loma, Patricia; Guzmán-Aránguez, Ana; Lara, María J Pérez de; Pintor, Jesús

doi:10.1016/j.exer.2015.02.014

Cited by 11 publications

(10 citation statements)

References 32 publications

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“…Naturally occurring diadenosine polyphosphates, such as Ap 4 A 58, activate P2YRs to regulate tear secretion and other functions. 45,[95][96][97] These dinucleotides are typically found in higher concentrations in eye diseases, such as Sjögren and non-Sjögren dry eye disease and glaucoma. It was suggested that lowering IOP by Ap 4 A is mediated by the P2X2R, causing acetylcholine release from nerve terminals that regulate ciliary processes.…”

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confidence: 99%

Ocular Purine Receptors as Drug Targets in the Eye

Civan

2016

Journal of Ocular Pharmacology and Therapeutics

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Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A 1 , A 2A , and A 3 . An A 1 AR agonist is in clinical trials for glaucoma, A 2A AR reduces neuroinflammation, A 3 AR protects retinal ganglion cells from apoptosis, and both A 3 AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y 2 and P2Y 6 , lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases.

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confidence: 99%

Ocular Purine Receptors as Drug Targets in the Eye

Civan

2016

Journal of Ocular Pharmacology and Therapeutics

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“…Indeed, when 5-MCA-NAT was topically applied after using diadenosine tetraphosphate, the amount of this melatonin analogue found within the eye was 3-fold the one measured when it was instilled alone [24]. This is indicating that *Corresponding author: Alkozi HA, Faculty of Optics and Optometry, Department of Biochemistry and Molecular Biology IV, Complutense University of Madrid, C/Arcos de Jalón 118, E-28037 Madrid, Spain, Tel: +34674467489; E-mail: Hawadh@ucm.es the transient elimination of the corneal tight junctions is an effective mechanism to permit the entrance of molecules into the eye [25].…”

Section: Short Commentarymentioning

confidence: 89%

Improving Melatonin Delivery Within the Eye

Alkozi¹,

Pintor²

2017

J Bioequiv Availab

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“…57 To determine whether the increase in barrier permeability induced by Ap 4 A could enhance drug delivery through the cornea, additional in vivo experiments with New Zealand white rabbits demonstrated the access of hypotensive compounds such as the melatonin analogue 5-MCA-NAT (5-methoxycarbonylamino-N-acetyltryptamine) and the adrenergic drugs brimonidine and timolol (Table 3). 57,58 Thus, when Ap 4 A was topically applied 2 h before drug instillation, increased levels of these compounds were found in the rabbit aqueous humor compared to the application of the drug alone and the hypotensive effect was also improved. Therefore, Ap 4 A application can improve ocular drug delivery and consequently therapeutic efficiency.…”

Section: Regulation Of Corneal Barrier Permeability By Ap 4 Amentioning

confidence: 89%

Understanding the Presence and Roles of Ap₄A (Diadenosine Tetraphosphate) in the Eye

Crooke

Guzmán-Aránguez

Carracedo

et al. 2017

Journal of Ocular Pharmacology and Therapeutics

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Diadenosine tetraphosphate abbreviated ApA is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of ApA are mostly carried out by P2Y receptors, but the participation of P2X2 and P2Y in processes such as the regulation of intraocular pressure (IOP), together with the P2Y, is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of ApA to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where ApA actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.

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Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency

Cited by 11 publications

References 32 publications

Ocular Purine Receptors as Drug Targets in the Eye

Ocular Purine Receptors as Drug Targets in the Eye

Improving Melatonin Delivery Within the Eye

Understanding the Presence and Roles of Ap₄A (Diadenosine Tetraphosphate) in the Eye

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Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency

Cited by 11 publications

References 32 publications

Ocular Purine Receptors as Drug Targets in the Eye

Ocular Purine Receptors as Drug Targets in the Eye

Improving Melatonin Delivery Within the Eye

Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the Eye

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Product

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Understanding the Presence and Roles of Ap₄A (Diadenosine Tetraphosphate) in the Eye