NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female
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 immu...
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doaj-c8ad68020627442291e9855b3080b4b02021-01-24T00:02:55ZengMDPI AGBiomolecules2218-273X2021-01-011114714710.3390/biom11020147NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and FemaleRomuald Brice Babou Kammoe0Gilles Kauffenstein1Julie Pelletier2Bernard Robaye3Jean Sévigny4Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, CanadaInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 10 rue Adrienne Bolland, 6041 Gosselies, BelgiumCentre de Recherche du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, CanadaNucleotides 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, P2Y<sub>1</sub>, and P2Y<sub>6</sub> receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (<i>Entpd1</i><sup>−/−</sup>) 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 P2Y<sub>6</sub> receptors, which was confirmed with <i>P2ry6</i><b><sup>−/−</sup></b> bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y<sub>2</sub> and/or P2Y<sub>4</sub>, and P2Y<sub>12</sub> in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, <i>Entpd1</i><b><sup>−/−</sup></b>, and <i>P2ry6</i><b><sup>−/−</sup></b> 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 P2Y<sub>6</sub> receptor activation were weaker in female bladders.https://www.mdpi.com/2218-273X/11/2/147NTPDase1extracellular nucleotidesbladdersmooth muscle cellscontractionP2Y<sub>6</sub> receptor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Romuald Brice Babou Kammoe Gilles Kauffenstein Julie Pelletier Bernard Robaye Jean Sévigny |
spellingShingle |
Romuald Brice Babou Kammoe Gilles Kauffenstein Julie Pelletier Bernard Robaye Jean Sévigny NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female Biomolecules NTPDase1 extracellular nucleotides bladder smooth muscle cells contraction P2Y<sub>6</sub> receptor |
author_facet |
Romuald Brice Babou Kammoe Gilles Kauffenstein Julie Pelletier Bernard Robaye Jean Sévigny |
author_sort |
Romuald Brice Babou Kammoe |
title |
NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female |
title_short |
NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female |
title_full |
NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female |
title_fullStr |
NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female |
title_full_unstemmed |
NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female |
title_sort |
ntpdase1 modulates smooth muscle contraction in mice bladder by regulating nucleotide receptor activation distinctly in male and female |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-01-01 |
description |
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, P2Y<sub>1</sub>, and P2Y<sub>6</sub> receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (<i>Entpd1</i><sup>−/−</sup>) 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 P2Y<sub>6</sub> receptors, which was confirmed with <i>P2ry6</i><b><sup>−/−</sup></b> bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y<sub>2</sub> and/or P2Y<sub>4</sub>, and P2Y<sub>12</sub> in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, <i>Entpd1</i><b><sup>−/−</sup></b>, and <i>P2ry6</i><b><sup>−/−</sup></b> 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 P2Y<sub>6</sub> receptor activation were weaker in female bladders. |
topic |
NTPDase1 extracellular nucleotides bladder smooth muscle cells contraction P2Y<sub>6</sub> receptor |
url |
https://www.mdpi.com/2218-273X/11/2/147 |
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