Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells

Abstract N-methyl-d-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In the present study, we examined the expression of NMDA receptor subunit mRNA and protein in human pulmonary art...

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Autores principales:	Yi Na Dong, Fu-Chun Hsu, Cynthia J. Koziol-White, Victoria Stepanova, Joseph Jude, Andrei Gritsiuta, Ryan Rue, Rosalind Mott, Douglas A. Coulter, Reynold A. Panettieri, Vera P. Krymskaya, Hajime Takano, Elena A. Goncharova, Dmitry A. Goncharov, Douglas B. Cines, David R. Lynch
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bd4b029a3e741f88fc9ecbfcf332be3
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spelling	oai:doaj.org-article:8bd4b029a3e741f88fc9ecbfcf332be32021-12-02T18:03:26ZFunctional NMDA receptors are expressed by human pulmonary artery smooth muscle cells10.1038/s41598-021-87667-02045-2322https://doaj.org/article/8bd4b029a3e741f88fc9ecbfcf332be32021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87667-0https://doaj.org/toc/2045-2322Abstract N-methyl-d-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In the present study, we examined the expression of NMDA receptor subunit mRNA and protein in human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry and immunoblotting. We demonstrate that both GluN1 and GluN2 subunit mRNAs are expressed in HPA. In addition, GluN1 and GluN2 (A–D) subunit proteins are expressed by human pulmonary artery smooth muscle cells (HPASMCs) in vitro and in vivo. These subunits localize on the surface of HPASMCs and form functional ion channels as evidenced by whole-cell patch-clamp electrophysiology and reduced phenylephrine-induced contractile responsiveness of human pulmonary artery by the NMDA receptor antagonist MK801 under hypoxic condition. HPASMCs also express high levels of serine racemase and vesicular glutamate transporter 1, suggesting a potential source of endogenous agonists for NMDA receptor activation. Our findings show HPASMCs express functional NMDA receptors in line with their effect on pulmonary vasoconstriction, and thereby suggest a novel therapeutic target for pharmacological modulations in settings associated with pulmonary vascular dysfunction.Yi Na DongFu-Chun HsuCynthia J. Koziol-WhiteVictoria StepanovaJoseph JudeAndrei GritsiutaRyan RueRosalind MottDouglas A. CoulterReynold A. PanettieriVera P. KrymskayaHajime TakanoElena A. GoncharovaDmitry A. GoncharovDouglas B. CinesDavid R. LynchNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi Na Dong Fu-Chun Hsu Cynthia J. Koziol-White Victoria Stepanova Joseph Jude Andrei Gritsiuta Ryan Rue Rosalind Mott Douglas A. Coulter Reynold A. Panettieri Vera P. Krymskaya Hajime Takano Elena A. Goncharova Dmitry A. Goncharov Douglas B. Cines David R. Lynch Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells
description	Abstract N-methyl-d-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In the present study, we examined the expression of NMDA receptor subunit mRNA and protein in human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry and immunoblotting. We demonstrate that both GluN1 and GluN2 subunit mRNAs are expressed in HPA. In addition, GluN1 and GluN2 (A–D) subunit proteins are expressed by human pulmonary artery smooth muscle cells (HPASMCs) in vitro and in vivo. These subunits localize on the surface of HPASMCs and form functional ion channels as evidenced by whole-cell patch-clamp electrophysiology and reduced phenylephrine-induced contractile responsiveness of human pulmonary artery by the NMDA receptor antagonist MK801 under hypoxic condition. HPASMCs also express high levels of serine racemase and vesicular glutamate transporter 1, suggesting a potential source of endogenous agonists for NMDA receptor activation. Our findings show HPASMCs express functional NMDA receptors in line with their effect on pulmonary vasoconstriction, and thereby suggest a novel therapeutic target for pharmacological modulations in settings associated with pulmonary vascular dysfunction.
format	article
author	Yi Na Dong Fu-Chun Hsu Cynthia J. Koziol-White Victoria Stepanova Joseph Jude Andrei Gritsiuta Ryan Rue Rosalind Mott Douglas A. Coulter Reynold A. Panettieri Vera P. Krymskaya Hajime Takano Elena A. Goncharova Dmitry A. Goncharov Douglas B. Cines David R. Lynch
author_facet	Yi Na Dong Fu-Chun Hsu Cynthia J. Koziol-White Victoria Stepanova Joseph Jude Andrei Gritsiuta Ryan Rue Rosalind Mott Douglas A. Coulter Reynold A. Panettieri Vera P. Krymskaya Hajime Takano Elena A. Goncharova Dmitry A. Goncharov Douglas B. Cines David R. Lynch
author_sort	Yi Na Dong
title	Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells
title_short	Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells
title_full	Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells
title_fullStr	Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells
title_full_unstemmed	Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells
title_sort	functional nmda receptors are expressed by human pulmonary artery smooth muscle cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8bd4b029a3e741f88fc9ecbfcf332be3
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Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells

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