Effects of diadenosine tetraphosphate on FGF9-induced chloride flux changes in achondroplastic chondrocytes

Huete, Fernando; Guzmán-Aránguez, Ana; Ortín, Javier; Hoyle, Charles H.V.; Pintor, Jesús

doi:10.1007/s11302-011-9234-y

Cited by 9 publications

(11 citation statements)

References 32 publications

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“…In this buffer, NaCl was replaced by an equimolar concentration of NaNO 3 (Panreac). Plates were then read on Fluoroskan FL fluorescence plate reader (Thermo Labsystems Inc., Waltham, MA) following the methodology described by Huete et al (2011).…”

Section: Methodsmentioning

confidence: 99%

Melatonin Receptors Trigger cAMP Production and Inhibit Chloride Movements in Nonpigmented Ciliary Epithelial Cells

Huete-Toral

Crooke

Martínez-Águila

et al. 2014

J Pharmacol Exp Ther

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Melatonin and its analog 5-MCA-NAT (5-methylcarboxyamino-N-acetyl tryptamine) are active compounds reducing intraocular pressure (IOP). This action is mediated through MT 2 and the putative MT 3 melatonin receptor, producing a transient reduction of IOP that lasts for a few hours and has not yet been characterized. The use of melatonin and its analog are causing a decrease in chloride efflux from rabbit nonpigmented epithelial cells (NPE), possibly explaining the decrease in IOP. Melatonin and 5-MCA-NAT inhibited rabbit NPE chloride release in a concentration-dependent manner, whereas the pD 2 values were between 4.5 6 1.2 and 4.4 6 1.0, respectively. Melatonin hypotensive action was enhanced by the presence of MT 2 antagonists, such as DH97 (N-pentanoyl-2-benzyltryptamine) and 4-P-P-DOT (4-phenyl-2-propionamidotetralin) and by the nonselective melatonin receptor antagonist luzindole. Prazosin (1.5 mM) partially reverses the melatonin action by acting as a selective MT 3 antagonist. However, at 15 nM it acts as an a-adrenergic receptor antagonist, enhancing the melatonin effect. Regarding the intracellular pathways triggered by melatonin receptors, neither phospholipase C/protein kinase C pathway nor the canonical reduction of intracellular cAMP was responsible for melatonin or 5-MCA-NAT actions. On the contrary, the application of these substances produced a concentration-dependent increase of cAMP, with pD 2 values of 4.6 6 0.2 and 4.9 6 0.7 for melatonin and 5-MCA-NAT, respectively. In summary, melatonin reduces the release of chloride concomitantly to cAMP generation. The reduction of Cl 2 secretion accounts for a decrease in the water outflow and therefore a decrease in aqueous humor production. This could be one of the main mechanisms responsible for the reduction of IOP after application of melatonin and 5-MCA-NAT.

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Section: Methodsmentioning

confidence: 99%

Melatonin Receptors Trigger cAMP Production and Inhibit Chloride Movements in Nonpigmented Ciliary Epithelial Cells

Huete-Toral

Crooke

Martínez-Águila

et al. 2014

J Pharmacol Exp Ther

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“…In other cellular models, achondroplastic chondrocytes, the effect of Ap 4 A was virtually identical. In this model, diadenosine tetraphosphate was also facilitating the efflux of chloride from these cells (Huete et al, 2011). Therefore, it seems that there is a coordinated action triggered by the P2Y 2 receptor after the stimulation by Ap 4 A that produces a mobilization of AQ1 towards the membrane and an increase in the Cl À efflux, which altogether, would be responsible for the P2Y 2 mediated elevation of IOP (Fig.…”

Section: Presence In the Aqueous Humourmentioning

confidence: 69%

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Carracedo

Crooke

Guzmán-Aránguez

et al. 2016

Progress in Retinal and Eye Research

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a b s t r a c tDinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap 4 A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y 2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp 4 U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

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“…In a later paper from this group, it was shown that P2Y 1 , P2Y 2 , P2Y 6 and P2Y 11 receptors were expressed by achondroplasic chondrocytes and that Ap 4 A was acting via these P2Y receptors [468]. In a more recent study, they showed that Ap 4 A reversed the morphological changes triggered by FGF9 and restored the chloride efflux, providing further evidence for the therapeutic potential of this dinucleotide in the treatment of dwarfism [469].…”

Section: Dwarfism (Achondroplasia)mentioning

confidence: 90%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

111

114

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It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

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Effects of diadenosine tetraphosphate on FGF9-induced chloride flux changes in achondroplastic chondrocytes

Cited by 9 publications

References 32 publications

Melatonin Receptors Trigger cAMP Production and Inhibit Chloride Movements in Nonpigmented Ciliary Epithelial Cells

Melatonin Receptors Trigger cAMP Production and Inhibit Chloride Movements in Nonpigmented Ciliary Epithelial Cells

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Purinergic signalling in the musculoskeletal system

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