Expression of the P2Y2 receptor on the rat ocular surface during a 1-year rearing period

Tanioka, Hidetoshi; Kuriki, Yumi; Sakamoto, Asuka; Katsuta, Osamu; Kawazu, Kouichi; Nakamura, Masatsugu

doi:10.1007/s10384-014-0342-4

Cited by 25 publications

(15 citation statements)

References 25 publications

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“…In exocrine tissues such as the lacrimal gland, RT-PCR and immunohistochemical analyses have identified P2Y 2 R expression in acinar and ductal cells (Kamada et al, 2012;Tanioka et al, 2014). While no functional response to the P2Y 2 R agonist UTP was observed in lacrimal acinar cells (Kamada et al, 2012), cultured lacrimal gland myoepithelial cells do exhibit increased [Ca 2+ ] i in response to extracellular UTP suggesting the presence of P2Y 2 or P2Y 4 receptors (Ohtomo et al, 2011).…”

Section: The Role Of P2 Receptors In Salivary Gland Functionmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren's syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

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Section: The Role Of P2 Receptors In Salivary Gland Functionmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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“…[16][17][18][19][20] Previous studies have shown that the stimulation of water and mucin secretion by diquafosol is related to the activation of phospholipase C through G proteins caused by the combination of diquafosol and P2Y 2 receptor, which consequently increases the concentration of calcium ion within the conjunctival epithelial cells and in GCs. 19,21 There is evidence demonstrating the improvement of aqueous tear secretion in animal models, [22][23][24] but no consensus on the efficacy of diquafosol as a clinical therapy for dry eye has been established.…”

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confidence: 99%

Efficacy and Safety of Topical Diquafosol Ophthalmic Solution for Treatment of Dry Eye

Chen

et al. 2015

Cornea

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Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

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“…It has been reported that the upregulated presence of P2Y 2 in the salivary glands increases the epidermal growth factor receptor (EGFR) e dependent expression of vascular cell adhesion molecule (VCAM)-1 and provokes the lymphocyte infiltration associated with the inflammation (Baker et al, 2008;Schrader et al, 2005). Meanwhile this receptor has not yet been located in the lacrimal gland, a similar effect could occur in Sj€ ogren Syndrome (Tanioka et al, 2014). Therefore, the high concentrations of diadenosine polyphosphates in Sj€ ogren syndrome patients would not be able to stimulate more lacrimation; they may even increase lymphocyte infiltration.…”

Section: Presence In Ocular Surface Pathologymentioning

confidence: 99%

“…Mechanical perturbations such as cell stretching (Patel et al, 2005), hydrostatic pressure (Cockayne et al, 2000;Ferguson et al, 1997;Knight and Burnstock, 2001) and compressive stress (Sauer et al, 2000) seem to be the candidates to trigger the release of these dinucleotides. The motion of the upper eyelid during the blinking process seems to be responsible for exerting shear stress on the epithelial cells and therefore increasing the levels of both diadenosine polyphosphates, concomitantly with the increase in the blinking frequency Rat, mouse and human Epithelial migration and stroma reorganization (Dutot et al, 2008;Groschel-Stewart et al, 1999;Mayo et al, 2008) P2Y 1 , P2Y 4 Rabbit, rat and human Undetermined (Klepeis et al, 2004;Pintor et al, 2004b) P2Y 2 Monkey, rabbit, rat and human Re-epithelization, corneal proliferation and corneal permeability increasing (Cowlen et al, 2003;Crooke et al, 2009;Klepeis et al, 2004;Loma et al, 2015b;Mediero et al, 2008;Pintor et al, 2004b) P2Y 6 Rabbit, rat and human Re-epithelization delay and corneal proliferation increasing (Klepeis et al, 2004;Mediero et al, 2006;Pintor et al, 2004b) P2Y 11 Rabbit and human Undetermined (Klepeis et al, 2004) Conjuctival Epithelium P2X7 Human Membrane permeabilization associated with iatrogenic pathology (Dutot et al, 2008) P2Y 2 Monkey, dog, rabbit and human Tear fluid and mucin secretion stimulation (Cowlen et al, 2003;Jumblatt and Jumblatt, 1998;Li et al, 2001;Murakami et al, 2000;Terakado et al, 2014) Rat and monkey Undetermined (Cowlen et al, 2003;Tanioka et al, 2014) described above were collected in subjects from 18 to 38 years old (Pintor et al, 2002a). The age is considere...…”

Section: Presence In the Tear Film Of Healthy Patientsmentioning

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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Expression of the P2Y2 receptor on the rat ocular surface during a 1-year rearing period

Abstract: We observed no significant age-related decrease was observed for P2Y2 receptor protein and mRNA expression on rat ocular surface tissues.

Cited by 25 publications

References 25 publications

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

Efficacy and Safety of Topical Diquafosol Ophthalmic Solution for Treatment of Dry Eye

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

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