Molecular and functional mapping of regional differences in P2Y receptor expression in the rat lens

Hu, Rebecca; Suzuki-Kerr, Haruna; Webb, Kevin F.; Rhodes, Jeremy D.; Collison, David; Duncan, G.; Donaldson, Paul J.

doi:10.1016/j.exer.2008.05.008

Cited by 12 publications

(16 citation statements)

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“…Similar spatial signalling differences have been observed in animal models. In the intact rat lens epithelium a regional pattern of functional receptor expression has also been found such that at the equator adrenaline dominated the Ca 2þ responses with only a relatively small response to ACh, while in the central anterior cells ACh produced the largest Ca 2þ increase with no response from adrenaline (Hu et al, 2008). Additionally, in chicken lens, activated EGFR was detected at the equator (annular pad) and superficial fibres but was absent in central anterior epithelial cells (Ireland, 2005).…”

Section: Spatial Differences In Ca 2þ Signalling In the Intact Lensmentioning

confidence: 89%

“…Clear differences between the species are apparent in these studies and no single animal species can be regarded as a complete (Churchill and Louis, 1997;Collison and Duncan, 2001;Hu et al, 2008). Also, even when the same agonist induces responses in different species, characterisation studies show that there are differences in receptor subtype expression.…”

Section: Heterogeneity In Receptor Expressionmentioning

confidence: 99%

“…The only attempts to study fibre cell Ca 2þ signalling have been carried out using either isolated fibre preparations (Srivastava et al, 1997) or lentoid bodies (Churchill and Louis, 2002). However, recent research carried out in the Duncan lab has been able to study dynamic changes in [Ca 2þ ] i in fibre cells in the intact lens (Hu et al, 2008). By confocal microscopy of fibre cells injected with the cell impermeant Ca 2þ indicator Fluo4, it was found that cortical fibre cells in intact rat lenses respond to both adrenergic and purinergic GPCR agonists with biphasic Ca 2þ responses.…”

Section: Ca 2þ Signalling In Lens Fibre Cellsmentioning

confidence: 99%

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The mechanisms of calcium homeostasis and signalling in the lens

Rhodes

Sanderson

2009

Experimental Eye Research

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a b s t r a c tExcessive Ca 2þ can be detrimental to cells and raised levels of Ca 2þ in human lenses with cortical cataract have been found to play a major role in the opacification process. Ca 2þ homeostasis is therefore, recognised as having fundamental importance in lens pathophysiology. Furthermore, Ca 2þ plays a central role as a second messenger in cell signalling and mechanisms have evolved which give cells exquisite control over intracellular Ca 2þ ([Ca 2þ ] i ) via an array of specialised regulatory and signalling proteins. In this review we discuss these mechanisms as they apply to the lens. Ca 2þ levels in human aqueous humour are approximately 1 mM and there is a large, 10,000 fold, inwardly directed gradient across the plasma membrane. In the face of such a large gradient highly efficient mechanisms are needed to maintain low [Ca 2þ ] i . The Na þ /Ca 2þ exchanger (NCX) and plasma membrane Ca 2þ -ATPase (PMCA) actively remove Ca 2þ from the cells, whereas the sarco(endo)plasmic reticulum Ca 2þ -ATPase (SERCA) sequesters Ca 2þ in the endoplasmic reticulum (ER) Ca 2þ store. In lens epithelial cells the dominant role is played by the ATPases, whilst in the fibre cells NCX activity appears to be more important. Usually, [Ca 2þ ] i can be increased in a number of ways. Ca 2þ influx through the plasma membrane, for example, is mediated by an array of channels with evidence in the lens for the presence of voltage-operated Ca 2þ channels (VOCCs), receptor-operated Ca 2þ channels (ROCCs) and channels mediating store-operated Ca 2þ entry (SOCE). Ca 2þ signalling is initiated via activation of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) of which the lens expresses a surprisingly diverse array responding to various neurotransmitters, hormones, growth factors, autocoids and proteases. Downstream of plasma membrane receptors are IP 3 -gated channels (IP 3 Rs) and ryanodine receptors (RYRs) located in the ER, which when activated cause a rapid increase in [Ca 2þ ] i and these have also been identified in the lens. Through an appreciation of the diversity and complexity of the mechanisms involved in Ca 2þ homeostasis in normal lens cells we move closer to an understanding of the mechanisms which mediate pathological Ca 2þ overload as occurs in the process of cataract formation.

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Section: Spatial Differences In Ca 2þ Signalling In the Intact Lensmentioning

confidence: 89%

Section: Heterogeneity In Receptor Expressionmentioning

confidence: 99%

Section: Ca 2þ Signalling In Lens Fibre Cellsmentioning

confidence: 99%

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The mechanisms of calcium homeostasis and signalling in the lens

Rhodes

Sanderson

2009

Experimental Eye Research

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“…The identification of P2Y receptors (P2Y 1 and P2Y 2 ) by RT-PCR and in situ hybridization in the lens has been described (Cowlen et al, 2003;Hu et al, 2008;Merriman-Smith et al, 1998). Because Ap 4 A is most representative of the dinucleotide in the aqueous humour, and its ability is known to stimulate both receptors, changes in Ap 4 A concentration could alter intracellular Ca 2þ concentration in cortical lens fibers.…”

Section: Putative Actions Of Dinucleotides In the Lensmentioning

confidence: 99%

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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“…Both P2X and P2Y receptor subtypes have been shown to be expressed on lens cells. P2Y 1 and P2Y 2 receptor mRNA was shown to be expressed on cortex fibre cells [5] and later also P2Y 4 and P2Y 6 receptor subtypes were identified on epithelial cells and peripheral fibre cells of the rat lens [6][7][8]. RT-PCR and Western blot analyses showed mRNA and protein for P2X1-7 receptors in the lens.…”

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confidence: 99%

Editorial

Burnstock

2011

Purinergic Signalling

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Molecular and functional mapping of regional differences in P2Y receptor expression in the rat lens

Cited by 12 publications

References 16 publications

The mechanisms of calcium homeostasis and signalling in the lens

The mechanisms of calcium homeostasis and signalling in the lens

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

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