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Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells.
Dong, Yi Na; Hsu, Fu-Chun; Koziol-White, Cynthia J; Stepanova, Victoria; Jude, Joseph; Gritsiuta, Andrei; Rue, Ryan; Mott, Rosalind; Coulter, Douglas A; Panettieri, Reynold A; Krymskaya, Vera P; Takano, Hajime; Goncharova, Elena A; Goncharov, Dmitry A; Cines, Douglas B; Lynch, David R.
Afiliación
  • Dong YN; Department of Pediatrics and Neurology, Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Hsu FC; Department of Pediatrics and Neurology, Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Koziol-White CJ; Rutgers Institute for Translational Medicine & Science, Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA.
  • Stepanova V; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Jude J; Rutgers Institute for Translational Medicine & Science, Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA.
  • Gritsiuta A; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Rue R; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Mott R; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Coulter DA; Department of Pediatrics and Neurology, Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Panettieri RA; Rutgers Institute for Translational Medicine & Science, Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA.
  • Krymskaya VP; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Takano H; Department of Pediatrics and Neurology, Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Goncharova EA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of California, Davis, Davis, CA, USA.
  • Goncharov DA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of California, Davis, Davis, CA, USA.
  • Cines DB; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Lynch DR; Department of Pediatrics and Neurology, Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 19104, USA. lynchd@pennmedicine.upenn.edu.
Sci Rep ; 11(1): 8205, 2021 04 15.
Article en En | MEDLINE | ID: mdl-33859248
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arteria Pulmonar / Receptores de N-Metil-D-Aspartato / Músculo Liso Vascular Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arteria Pulmonar / Receptores de N-Metil-D-Aspartato / Músculo Liso Vascular Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido