Distribution of P2x Receptors in the Urinary Bladder and the Ureter of the Rat

Lee, Hye Yeon; Bardini, Michelle; Burnstock, Geoffrey

doi:10.1016/s0022-5347(05)67618-5

Cited by 183 publications

(89 citation statements)

References 33 publications

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“…7d). Consistent with these results, the intracellular localization of the P2X7 receptor is well documented in other models [37–39]. The characteristic appearance as stained dots was reported to be distributed close to the membrane but also colocalized with the endoplasmatic reticulum [40].…”

Section: Resultssupporting

confidence: 78%

Porphyromonas gingivalis Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

et al. 2014

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Porphyromonas gingivalis is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-interleukin (IL)-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP (eATP). Here, we investigated the role of P. gingivalis fimbriae in eATP-induced IL-1β release. Bone marrow-derived macrophages (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with P. gingivalis (381) or isogenic fimbria-deficient (DPG3) strain with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent on K⁺ efflux and Ca²⁺-independent phospholipase A₂ activity. Accordingly, non-fimbriated P. gingivalis failed to inhibit apoptosis via the eATP/P2X7 pathway. Furthermore, P. gingivalis-driven stimulation of IL-1β was Toll-like receptor 2 and MyD88 dependent, and not associated with fimbria expression. Fimbria-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of P. gingivalis stimulation, which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a marked focus formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by P. gingivalis fimbriae in a P2X7-dependent manner.

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Section: Resultssupporting

confidence: 78%

Porphyromonas gingivalis Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

et al. 2014

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“…Nuclear/perinuclear localization of the wild-type P2X 7 was previously described in epithelial (40,41), neuronal (e.g. Ref.…”

Section: Discussionmentioning

confidence: 96%

A Truncated P2X7 Receptor Variant (P2X7-j) Endogenously Expressed in Cervical Cancer Cells Antagonizes the Full-length P2X7 Receptor through Hetero-oligomerization

Li²,

Wang

et al. 2006

Journal of Biological Chemistry

142

262

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A truncated naturally occurring variant of the human receptor P2X 7 was identified in cancer cervical cells. The novel protein (P2X 7-j ), a polypeptide of 258 amino acids, lacks the entire intracellular carboxyl terminus, the second transmembrane domain, and the distal third of the extracellular loop of the full-length P2X 7 receptor. The P2X 7-j was expressed in the plasma membrane; it showed diminished ligand-binding and channel function capacities and failed to form pores and mediate apoptosis in response to treatment with the P2X 7 receptor agonist benzoyl-ATP. The P2X 7-j interacted with the full-length P2X 7 in a manner suggesting heterooligomerization and blocked the P2X 7 -mediated actions. Interestingly, P2X 7-j immunoreactivity and mRNA expression were similar in lysates of human cancer and normal cervical tissues, but fulllength P2X 7 immunoreactivity and mRNA expression were higher in normal than in cancer tissues, and cancer tissues lacked 205-kDa P2X 7 immunoreactivity suggesting lack of P2X 7 homo(tri)-oligomerization. These results identify a novel P2X 7 variant with apoptosis-inhibitory actions, and demonstrate a distinct regulatory property for a truncated variant to antagonize its full-length counterpart through hetero-oligomerization. This may represent a general paradigm for regulation of a protein function by its variant.The receptor P2X 7 belongs to the P2X subfamily of P2 nucleotide receptors (1, 2), which are membrane-bound, ligand-operated channels (3-5). ATP is the naturally occurring ligand for the P2X 7 and activation of the receptor by brief exposure to extracellular ATP opens cation channels that allow Ca 2ϩ , Na ϩ , and K ϩ influx (6). Longer exposure to ATP allows passage of cations with progressively larger diameters, up to 900 Da, through formation of pores (7). The mechanism of pore formation is unclear, and opinions vary between decreased filter selectivity of existing channels (8) to rearrangement of receptor molecules (9). P2X 7 receptors function in a cell-specific manner and effects of receptor activation are determined by receptor expression (10), trafficking and plasma membrane localization (11-13), oligomerization (5), and postactivation internalization, recycling, and degradation (14). Expression of P2X 7 can be regulated hormonally; in human cervical epithelial cells epinephrine down-regulates expression of the glycosylated form of the P2X 7 and increases receptor degradation, and the effects can be potentiated by epidermal growth factor (15). Evidence for the physiological role of the P2X 7 comes from studies of P2X 7 -deficient mice, indicating its role in inflammatory (16) and immune processes (17). Epithelial cells of the female lower reproductive tract express the P2X 7 (18), and in human cervical epithelial cells ligand binding induces apoptosis by a mechanism that involves pore formation, augmented calcium influx, and calcium-dependent activation of the apoptotic mitochondrial pathway (19,20). Because human cervical epithelial cells secrete ATP into the extra...

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“…P2X 7 immunoreactivity found in the cytoplasm may reflect newly formed receptor en route to be inserted into the plasma membrane, or postactivation internalized, degraded, or recycled receptor [20]. Perinuclear/nuclear P2X 7 immunoreactivity was previously described in epithelial [28,43,44] and other types of cells [45,46], but its biological significance remains unclear. It is unlikely an artifact (i.e., non-specific binding) because it was found in tissues processed in parallel with those not found to express this type of signal (present study).…”

Section: Discussionmentioning

confidence: 98%

P2X7 receptor expression is decreased in epithelial cancer cells of ectodermal, uro-genital sinus, and distal paramesonephric duct origin

Zhou

et al. 2009

Purinergic Signalling

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The P2X(7) receptor is an important regulator of epithelial cell growth. The aim of the present study was to better understand the biological significance of P2X(7) receptor expression in normal and cancer human epithelial tissues. P2X(7) receptor and messenger RNA (mRNA) levels were determined in human tissues containing epithelial dysplastic, pre- or early cancerous, and cancer cells, and the levels were compared to those in the corresponding normal epithelial cells within the same tissue of the same case. P2X(7) receptor levels were determined by quantification of immunoreactivity specific to the functional (full-length) P2X(7) receptor, and P2X(7) mRNA levels were determined by real-time polymerase chain reaction. P2X(7) receptor levels in cancer cells were similar (colon adenocarcinoma) or greater (thyroid papillary carcinoma) than those in the corresponding normal cells. In contrast, in cancer cells of the ectocervix (squamous), endocervix and endometrium (adenocarcinoma), urinary bladder (transitional cell carcinoma), and breast (ductal and lobular adenocarcinomas), P2X(7) receptor levels were lower by about twofold than those in the corresponding normal epithelial cells. Similarly, P2X(7) mRNA levels were lower in uterine, bladder, and breast cancer epithelial tissues by about fourfold than those in the corresponding normal tissues. In addition, P2X(7) receptor levels were decreased already in dysplastic ectocervical cells and pre- or early cancerous endometrial and bladder cells. The data suggest that in epithelia originating from the ectoderm, the uro-genital sinus, and the distal paramesonephric duct, decreased expression of the P2X(7) receptor precedes or coincides with neoplastic changes in those tissues.

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Distribution of P2x Receptors in the Urinary Bladder and the Ureter of the Rat

Abstract: Having established the distribution of P2X receptors in normal animal bladder and ureter tissue, it is now possible to perform comparable investigations on normal and diseased human tissue to establish a possible role of P2X receptors in pathogenic events.

Cited by 183 publications

References 33 publications

<b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

<b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

A Truncated P2X7 Receptor Variant (P2X7-j) Endogenously Expressed in Cervical Cancer Cells Antagonizes the Full-length P2X7 Receptor through Hetero-oligomerization

P2X7 receptor expression is decreased in epithelial cancer cells of ectodermal, uro-genital sinus, and distal paramesonephric duct origin

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