NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female
Open Access
- 23 January 2021
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 11 (2), 147
- https://doi.org/10.3390/biom11020147
Abstract
Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders.This publication has 71 references indexed in Scilit:
- Nerve-evoked purinergic signalling suppresses action potentials, Ca2+flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscleJournal Of Physiology-London, 2009
- Thromboxane A2 Receptor Activates a Rho-associated Kinase/LKB1/PTEN Pathway to Attenuate Endothelium Insulin SignalingOnline Journal of Public Health Informatics, 2009
- Overexpression of CD39/nucleoside triphosphate diphosphohydrolase-1 decreases smooth muscle cell proliferation and prevents neointima formation after angioplastyJournal of Thrombosis and Haemostasis, 2008
- P2 receptors in cardiovascular regulation and diseasePurinergic Signalling, 2007
- International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to TherapyPharmacological Reviews, 2006
- Physiological roles for ecto-5’-nucleotidase (CD73)Purinergic Signalling, 2006
- The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significancePurinergic Signalling, 2006
- Nucleoside triphosphate diphosphohydrolase‐2 is the ecto‐ATPase of type I cells in taste budsJournal of Comparative Neurology, 2006
- Cloning and characterization of the ecto-nucleotidase NTPDase3 from rat brain: Predicted secondary structure and relation to other members of the E-NTPDase family and actinPurinergic Signalling, 2005
- Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8Purinergic Signalling, 2005