Characterization of P2X<sub>7</sub>Purinergic Receptors and Their Function in Rat Lacrimal Gland

Hodges, Robin R.; Vrouvlianis, Joanna; Shatos, Marie A.; Dartt, Darlene A.

doi:10.1167/iovs.09-3670

Cited by 27 publications

(39 citation statements)

References 27 publications

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“…P2X7 has been reported in both the acinar and ductal cells of rat lacrimal gland [47]. As observed for pancreas, we found a greater number of adipocytes in the extraorbital lacrimal glands of male mice at 12 months of age (Fig.…”

Section: Histological Differences In the Pancreases Of Wt And Ko Micesupporting

confidence: 82%

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Beaucage

Xiao

Pollmann

et al. 2013

Purinergic Signalling

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The P2X7 receptor is an ATP-gated cation channel expressed by a number of cell types. We have shown previously that disruption of P2X7 receptor function results in downregulation of osteogenic markers and upregulation of adipogenic markers in calvarial cell cultures. In the present study, we assessed whether loss of P2X7 receptor function results in changes to adipocyte distribution and lipid accumulation in vivo. Male P2X7 loss-of-function (KO) mice exhibited significantly greater body weight and epididymal fat pad mass than wild-type (WT) mice at 9 months of age. Fat pad adipocytes did not differ in size, consistent with adipocyte hyperplasia rather than hypertrophy. Histological examination revealed ectopic lipid accumulation in the form of adipocytes and/or lipid droplets in several non-adipose tissues of older male KO mice (9-12 months of age). Ectopic lipid was observed in kidney, extraorbital lacrimal gland and pancreas, but not in liver, heart or skeletal muscle. Specifically, lacrimal gland and pancreas from 12-month-old male KO mice had greater numbers of adipocytes in perivascular, periductal and acinar regions. As well, lipid droplets accumulated in the renal tubular epithelium and lacrimal acinar cells. Blood plasma analyses revealed diminished total cholesterol levels in 9-and 12-month-old male KO mice compared with WT controls. Interestingly, no differences were observed in female mice. Moreover, there were no significant differences in food consumption between male KO and WT mice. Taken together, these data establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism in an age-and sex-dependent manner.

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Section: Histological Differences In the Pancreases Of Wt And Ko Micesupporting

confidence: 82%

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Beaucage

Xiao

Pollmann

et al. 2013

Purinergic Signalling

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“…Activation of P2X7 receptors in rat lacrimal gland by the nucleotide (benzoylbenzoyl)adenosine 59triphosphate (BzATP) increased intracellular calcium and stimulated protein secretion (Hodges et al, 2009). Furthermore, the expression of specific tear proteins such as secreted mucins can also be modified by nucleotides.…”

Section: Nucleotides At the Ocular Surfacementioning

confidence: 99%

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

Guzmán-Aránguez

Santano

Martín-Gil

et al. 2013

J Pharmacol Exp Ther

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The presence and activity of nucleotides and dinucleotides in the physiology of most, if not all, organisms, from bacteria to humans, have been recognized by the scientific community, and the eye is no exception. Nucleotides in the dynamic fluids interact with many ocular structures, such as the tears and aqueous humor. Moreover, high concentrations of nucleotides in these secretions may reflect disease states such as dry eye and glaucoma. Apart from the nucleotide concentration in these fluids, P2 purinergic receptors have been described on the ocular surface (cornea and conjunctiva), anterior pole (ciliary body, trabecular meshwork), and posterior pole (retina). P2X and P2Y purinergic receptors are essential in maintaining the homeostasis of ocular processes, such as tear secretion, aqueous humor production, or retinal modulation. When they are functioning properly, they allow the eye to do its job (to see), but in some cases, a lack or an excess of nucleotides or a malfunction in the corresponding purinergic receptors leads to disease. This Perspective is focused on the nucleotides and dinucleotides and the P2 purinergic receptors in the eye and how they contribute to normal and disease states. We also emphasize the action of nucleotides and their receptors and antagonists as potential therapeutic agents.

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“…It has been reported that acinar cells express ionotropic P2X purinoceptors (Hodges et al 2009(Hodges et al , 2011Dartt and Hodges 2011a, b), but there have been few studies of metabotropic P2Y receptors in the lacrimal gland. We therefore analyzed the potential contribution of P2 receptors to ATP-induced [Ca 2+ ] i increases in lacrimal gland acinar cells using receptor-speciWc agonists and antagonists.…”

Section: Evect Of Atp and Atp Analogs On [Ca 2+ ] I Dynamicsmentioning

confidence: 99%

“…Recent studies have demonstrated that the P2X 7 receptor is expressed in rat lacrimal gland (Hodges et al 2009(Hodges et al , 2011Dartt and Hodges 2011a, b) in addition to purinergic P2X 1-4,6 receptors (Hodges et al 2009). Hodges et al (2011) has indicated that ATP can induce an increase in [Ca 2+ ] i and in protein secretion via P2X 3 and P2X 7 receptors (Hodges et al 2011).…”

Section: Introductionmentioning

confidence: 99%

P2Y purinoceptors induce changes in intracellular calcium in acinar cells of rat lacrimal glands

Kamada

Saino

Oikawa

et al. 2011

Histochem Cell Biol

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Adenosine 5'-triphosphate (ATP) is an extracellular signal that regulates various cellular functions. Cellular secretory activities are enhanced by ATP as well as by cholinergic and adrenergic stimuli. The present study aimed to determine which purinoceptors play a role in ATP-induced changes in the intracellular concentration of calcium ions ([Ca²⁺](i)) and in the fine structure of acinar cells of rat lacrimal glands. ATP induced exocytotic structures, vacuolation and an increase in [Ca²⁺](i) in acinar cells. The removal of extracellular Ca²⁺ or the use of Ca²⁺ channel blockers partially inhibited the ATP-induced [Ca²⁺](i) increase. U73122 (an antagonist of PLC) and heparin (an antagonist of IP₃ receptors) did not completely inhibit the ATP-induced [Ca²⁺](i) increase. P1 purinoceptor agonists did not induce any changes in [Ca²⁺](i), whereas suramin (an antagonist of P2 receptors) completely inhibited ATP-induced changes in [Ca²⁺](i). A P2Y receptor agonist, 2-MeSATP, induced a strong increase in [Ca²⁺](i), although UTP (a P2Y₂,₄,₆ receptor agonist) had no effect, and reactive blue 2 (a P2Y receptor antagonist) resulted in partial inhibition. The potency order of ATP analogs (2-MeSATP > ATP >>> UTP) suggested that P2Y₁ played a significant role in the cellular response to ATP. BzATP (a P2X₇ receptor agonist) induced a small increase in [Ca²⁺](i), but α,β-meATP (a P2X₁,₃ receptor agonist) had no effect. RT-PCR indicated that P2X₂,₃,₄,₅,₆,₇ and P2Y₁,₂,₄,₁₂,₁₄ are expressed in acinar cells. In conclusion, the response of acinar cells to ATP is mediated by P2Y (especially P2Y₁) as well as by P2X purinoceptors.

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Characterization of P2X₇Purinergic Receptors and Their Function in Rat Lacrimal Gland

Cited by 27 publications

References 27 publications

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

P2Y purinoceptors induce changes in intracellular calcium in acinar cells of rat lacrimal glands

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Characterization of P2X7Purinergic Receptors and Their Function in Rat Lacrimal Gland

Cited by 27 publications

References 27 publications

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

P2Y purinoceptors induce changes in intracellular calcium in acinar cells of rat lacrimal glands

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Characterization of P2X₇Purinergic Receptors and Their Function in Rat Lacrimal Gland