Prostaglandins Differentially Regulate the Constitutive and Mechanosensitive Release of Soluble Nucleotidases in the Urinary Bladder Mucosa
Abstract
1. Introduction
2. Results
2.1. Influences of Endogenous Activators of EP Prostanoid Receptors on Spontaneous Release of s-NTDs
2.2. Influences of Endogenous Activators of EP Prostanoid Receptors on Distention-Induced Release of s-NTDs
2.3. Influences of Endogenous Activators of Prostanoid DP and FP Receptors on Spontaneous and Distention-Induced Release of s-NTDs
2.4. Influences of Endogenous Activators of Prostanoid IP Receptors on Spontaneous and Distention-Induced Release of s-NTDs
2.5. Effects of COX Inhibition on Spontaneous and Distention-Induced Release of s-NTDs
2.6. Effects of Exogenous PGI2 and TXA2 Analog on the Spontaneous and Distention-Induced Release of s-NTDs
2.7. Effects of Exogenous PGE2 on the Spontaneous Release of s-NTDs and Involvement of EP Prostanoid Receptors
2.8. Effects of Exogenous PGE2 on Distention-Induced Release of s-NTDs and Involvement of EP Prostanoid Receptors
2.9. Effects of FP Receptor Blockade on the Effects of Exogenous PGE2 and PGF2α on Spontaneous and Distention-Induced Release of s-NTDs
2.10. Effects of Exogenous PGD2 on Spontaneous Release of s-NTDs and Involvement of DP Prostanoid Receptors
2.11. Effects of Exogenous PGD2 on Distention-Induced Release of s-NTDs and Involvement of DP Prostanoid Receptors
3. Discussion
4. Materials and Methods
4.1. Animal Model
4.1.1. Euthanasia and Tissue Collection
4.1.2. Ethical Approval
4.2. Ex Vivo Detrusor-Free Bladder Preparation
4.3. Soluble Nucleotidase (s-NTD) Activity in Concentrated Extraluminal Solutions
4.3.1. Collection of Extraluminal Solutions Containing s-NTDs
4.3.2. Concentration of Extraluminal Solutions Containing s-NTDs
4.3.3. Time Course of Extracellular eATP Degradation by s-NTDs in cELS of Nondistended and Distended LP
4.4. HPLC Analysis of 1,N6-Etheno-Purines
4.5. Drugs
4.6. Statistical Analysis of Data
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Name | Type | Concentration (μM) | Vehicle |
---|---|---|---|
PGE2 | EP1-4 receptor agonist | 10 | DMSO |
PGD2 | DP1, DP2 receptor agonist | 10 | DMSO |
PGF2α | FP receptor agonist | 10 | DMSO |
PGI2 | IP receptor agonist | 10 | DMSO |
U46619 | TP (TXA2) receptor agonist | 10 | DMSO |
SC51322 | EP1 receptor antagonist | 1 | DMSO |
PF04418948 | EP2 receptor antagonist | 1 | DMSO |
L-798,106 | EP3 receptor antagonist | 0.25 | DMSO |
L-161,982 | EP4 receptor antagonist | 1 | DMSO |
S-5751 | DP1 receptor antagonist | 1 | DMSO |
OC000459 | DP2 receptor antagonist | 10 | DMSO |
AMG 853 | DP1/DP2 receptor antagonist | 1 | DMSO |
AL8810 | FP receptor antagonist | 10 | DMSO |
RO1138452 | IP receptor antagonist | 10 | DMSO |
Indomethacin | COX1/COX2 inhibitor | 10 | DMSO |
Vehicle (n = 6) | PGI2 (n = 4) | RO1138452 (n = 6) | RO1138452 + PGI2 (n = 4) | U46619 (n = 4) | Indomethacin (n = 4) | |
---|---|---|---|---|---|---|
eATP | 56.67 ± 5.8 | 59.69 ± 8.16 | 54.39 ± 16.58 | 55.79 ± 10.63 | 53.63 ± 10.26 | 57.52 ± 11.21 |
eADP | 33.79 ± 3.79 | 31.35 ± 5.08 | 34.71 ± 10.33 | 33.78 ± 7.12 | 35.24 ± 5.47 | 32.40 ± 7.79 |
eAMP | 7.55 ± 1.69 | 6.39 ± 0.92 | 8.12 ± 3.62 | 7.94 ± 2.64 | 8.40 ± 2.18 | 9.00 ± 2.66 |
eADO | 1.99 ± 0.62 | 2.57 ± 2.17 | 2.77 ± 2.83 | 2.49 ± 1.02 | 2.74 ± 2.78 | 1.08 ± 1.00 **** |
Vehicle (n = 6) |
PGI2 (n = 4) |
RO1138452 (n = 6) |
RO1138452 + PGI2 (n = 4) |
U46619 (n = 4) |
Indomethacin (n = 4) | |
---|---|---|---|---|---|---|
eATP | 22.53 ± 9.09 | 27.53 ± 11.58 | 13.53 ± 9.38 | 23.32 ± 12.80 | 19.42 ± 8.00 | 30.70 ± 13.90 |
eADP | 48.63 ± 2.83 | 47.41 ± 2.70 | 45.86 ± 3.37 | 46.77 ± 2.42 | 47.46 ± 2.16 | 46.37 ± 5.84 |
eAMP | 19.33 ± 3.60 | 15.53 ± 2.17 | 21.14 ± 5.78 | 20.25 ± 8.58 | 21.56 ± 2.98 | 18.32 ± 4.99 |
eADO | 9.50 ± 4.55 | 9.23 ± 7.80 | 19.47 ± 12.32 *** | 9.66 ± 5.70 | 11.56 ± 8.64 | 4.61 ± 3.33 **** |
PGE2 | PGF2α | PGD2 | PGI2 | |
---|---|---|---|---|
Nondistended LP | ↑ EP2, ↑ EP3 | → | → | → |
Distended LP | → | → | → | ↓ IP |
PGE2 | PGF2α | PGD2 | PGI2 | TXA2 | |
---|---|---|---|---|---|
Nondistended LP | ↑ EP3, ↑ EP4, ↑ FP | ↑ FP | ↑ DP2 | → | → |
Distended LP | ↑ EP1, ↑ EP2, ↑ EP3, ↑ EP4, ↑ FP | → | ↑ DP1, ↑ DP2, ↓“X” | → | → |
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Gutierrez Cruz, A.; Borhani Peikani, M.; Beaulac, T.D.; Mutafova-Yambolieva, V.N. Prostaglandins Differentially Regulate the Constitutive and Mechanosensitive Release of Soluble Nucleotidases in the Urinary Bladder Mucosa. Int. J. Mol. Sci. 2025, 26, 131. https://doi.org/10.3390/ijms26010131
Gutierrez Cruz A, Borhani Peikani M, Beaulac TD, Mutafova-Yambolieva VN. Prostaglandins Differentially Regulate the Constitutive and Mechanosensitive Release of Soluble Nucleotidases in the Urinary Bladder Mucosa. International Journal of Molecular Sciences. 2025; 26(1):131. https://doi.org/10.3390/ijms26010131
Chicago/Turabian StyleGutierrez Cruz, Alejandro, Mahsa Borhani Peikani, Tori D. Beaulac, and Violeta N. Mutafova-Yambolieva. 2025. "Prostaglandins Differentially Regulate the Constitutive and Mechanosensitive Release of Soluble Nucleotidases in the Urinary Bladder Mucosa" International Journal of Molecular Sciences 26, no. 1: 131. https://doi.org/10.3390/ijms26010131
APA StyleGutierrez Cruz, A., Borhani Peikani, M., Beaulac, T. D., & Mutafova-Yambolieva, V. N. (2025). Prostaglandins Differentially Regulate the Constitutive and Mechanosensitive Release of Soluble Nucleotidases in the Urinary Bladder Mucosa. International Journal of Molecular Sciences, 26(1), 131. https://doi.org/10.3390/ijms26010131