Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria
Abstract
:1. Introduction
2. Results
2.1. Capsaicin Does Not Alter the Spontaneous and the Distention-Induced Release of s-ENTDs in LP
2.2. Neural Blockade with Tetrodotoxin (TTX) Has No Effect on the Spontaneous Release of s-ENTDs but Increases the Distention-Induced Release of s-ENTDs in LP
2.3. Neural Blockade with ω-Conotoxin (ω-CtxGVIA) Increases Both the Spontaneous and the Distention-Induced Release of sNTDs
2.4. Inhibition of PIEZO Channels Has No Effect on the Spontaneous Release of s-ENTDs, but Increases the Distention-Induced Release of s-ENTDs in LP
2.5. Inhibition of TRPC1 and TRPC6 Channels Have Weak Effect on the Spontaneous and Distention-Induced Release of s-ENTDs in LP
2.6. Inhibition of Receptors for Sensory Neuropeptides Affects Differentially the Release of s-ENTDs in LP
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Ex Vivo Detrusor-Free Bladder Preparation
4.3. General Experimental Protocol
4.4. Preparation of Extraluminal Samples for Measuring Soluble Nucleotidase Activities in the LP
4.5. Time-Course of ATP Hydrolysis in Concentrated ELS of Nondistended and Distended Preparations
4.6. Synthesis of 1,N6-etheno-ATP Substrate
4.7. HPLC Analysis of 1,N6-etheno-nucleotides and 1,N6-etheno-nucleosides
4.8. Statistical Analyses
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug | Mechanism of Action | Working Concentration (µM) | Vehicle | Vendor |
---|---|---|---|---|
BI-749327 | TRPC6 inhibitor | 1 | DMSO 0.2% | MedChemExpress, Monmouth Junction, NJ, USA |
Capsaicin | TRPV1 channel agonist | 1 | DMSO 0.1% | Tocris Biosciences, Minneapolis, MN, USA |
ω-CtxGVIA | Cav2.2 (N-type) Ca2+ channel inhibitor | 0.1 | KBS | Tocris Biosciences |
D-GsMTx4 | PIEZO inhibitor | 1 | KBS | Tocris Biosciences |
GSK 1702934A | TRPC3/6 activator | 3 | DMSO 0.2% | Tocris Biosciences |
GSK 2833503A | TRPC3/6 inhibitor | 1 | DMSO 0.2% | Tocris Biosciences |
GsMTx4 | PIEZO inhibitor | 1 | KBS | Tocris Biosciences |
MEN 10376 | NK2 receptor antagonist | 10 | KBS | Cayman Chemicals, Ann Arbor, MI, USA |
TTX | Fast Na+ channel inhibitor | 0.5 | KBS | Alomone Labs, Jerusalem, Israel |
PACAP6-38 | PAC1 receptor antagonist | 0.3 | KBS | Tocris Biosciences |
Pico145 | TRPC1,4,5 inhibitor | 1 | DMSO 0.2% | MedChemExpress |
Yoda1 | PIEZO1 activator | 40 | DMSO 0.2% | Tocris Biosciences |
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Aresta Branco, M.S.L.; Gutierrez Cruz, A.; Borhani Peikani, M.; Mutafova-Yambolieva, V.N. Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria. Int. J. Mol. Sci. 2023, 24, 7322. https://doi.org/10.3390/ijms24087322
Aresta Branco MSL, Gutierrez Cruz A, Borhani Peikani M, Mutafova-Yambolieva VN. Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria. International Journal of Molecular Sciences. 2023; 24(8):7322. https://doi.org/10.3390/ijms24087322
Chicago/Turabian StyleAresta Branco, Mafalda S. L., Alejandro Gutierrez Cruz, Mahsa Borhani Peikani, and Violeta N. Mutafova-Yambolieva. 2023. "Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria" International Journal of Molecular Sciences 24, no. 8: 7322. https://doi.org/10.3390/ijms24087322