Role of Pannexin 1, P2X7, and CFTR in ATP Release and Autocrine Signaling by Principal Cells of the Epididymis
Bibliographic record
Abstract
Extracellular adenosine triphosphate (ATP) is a signaling molecule that acts as a paracrine and autocrine modulator of cell function. Here, we characterized the role of luminal ATP in the regulation of epithelial principal cells (PCs) in the epididymis, an understudied organ that plays crucial roles in male reproduction. We previously showed that ATP secretion by PCs is part of a complex communication system that ensures the establishment of an optimal luminal acidic environment in the epididymis. However, the molecular mechanisms regulating ATP release and the role of ATP-mediated signaling in PCs acidifying functions are not fully understood. In other cell types, pannexin 1 (PANX-1) has been associated with ATP-induced ATP release through the interaction with the purinergic P2X7 receptor. Here, we show that PANX-1 and P2X7 are located in the apical membrane of PCs in the mouse epididymis. Functional analysis using the immortalized epididymal PC cell line (DC2) and the mouse epididymis perfused in vivo showed that (1) PANX-1 and P2X7 participate in ATP release by DC2 cells, together with cystic fibrosis transmembrane conductance regulator (CFTR); (2) several ATP-activated P2Y and P2X purinergic receptors are expressed in DC2 cells; (3) the nonhydrolyzable ATP analog ATPγS induces a dose-dependent increase in intracellular Ca2+ concentration in DC2 cells, a process that is mainly mediated by P2X7; and (4) perfusion of the epididymal lumen in vivo with ATPγS induces the internalization of apical sodium-hydrogen exchanger 3 (NHE3) in PCs. Altogether, this study shows that luminal ATP, regulated by CFTR, PANX-1, and P2X7, modulates sodium-proton exchange in PCs in an autocrine manner through activation of purinergic receptor-mediated intracellular calcium signaling.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".