Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria
The urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential f...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Mafalda S. L. Aresta Branco Alejandro Gutierrez Cruz Mahsa Borhani Peikani Violeta N. Mutafova-Yambolieva |
| author_facet | Mafalda S. L. Aresta Branco Alejandro Gutierrez Cruz Mahsa Borhani Peikani Violeta N. Mutafova-Yambolieva |
| author_sort | Mafalda S. L. Aresta Branco |
| collection | DOAJ |
| description | The urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium/lamina propria (LP) in a mechanosensitive manner. Using 1,N<sup>6</sup>-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and ω-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling. |
| first_indexed | 2024-03-11T04:56:39Z |
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| language | English |
| last_indexed | 2024-03-11T04:56:39Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f851e08c90fe43ff8efeaaf2f64654942023-11-17T19:38:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248732210.3390/ijms24087322Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina PropriaMafalda S. L. Aresta Branco0Alejandro Gutierrez Cruz1Mahsa Borhani Peikani2Violeta N. Mutafova-Yambolieva3Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USADepartment of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USADepartment of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USADepartment of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USAThe urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium/lamina propria (LP) in a mechanosensitive manner. Using 1,N<sup>6</sup>-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and ω-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling.https://www.mdpi.com/1422-0067/24/8/7322ATPurotheliumectonucleotidasesPIEZOPAC1 receptorsensory neuropeptides |
| spellingShingle | Mafalda S. L. Aresta Branco Alejandro Gutierrez Cruz Mahsa Borhani Peikani Violeta N. Mutafova-Yambolieva 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 ATP urothelium ectonucleotidases PIEZO PAC1 receptor sensory neuropeptides |
| title | Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria |
| title_full | Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria |
| title_fullStr | Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria |
| title_full_unstemmed | Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria |
| title_short | Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria |
| title_sort | sensory neurons piezo channels and pac1 receptors regulate the mechanosensitive release of soluble ectonucleotidases in the murine urinary bladder lamina propria |
| topic | ATP urothelium ectonucleotidases PIEZO PAC1 receptor sensory neuropeptides |
| url | https://www.mdpi.com/1422-0067/24/8/7322 |
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