title: γ-Aminobutyric Acid Is Synthesized and Released by the Endothelium: Potential Implications.
abstract: BACKGROUND
  Gamma aminobutyric acid (GABA), a neurotransmitter of the central nervous system, is found in the systemic circulation of humans at a concentration between 0.5 and 3 μmol/L. However, the potential source of circulating GABA and its significance on the vascular system remains unknown. We hypothesized that endothelial cells (ECs) may synthesize and release GABA to modulate some functions in the EC and after its release into the circulation.
  
  
  OBJECTIVE
  To assess whether GABA is synthesized and released by the EC and its potential functions.
  
  
  RESULTS
  Utilizing the human umbilical vein ECs and aortic ECs, we demonstrated for the first time that ECs synthesize and release GABA from [1-(14)C]glutamate. Localization of GABA and the presence of the GABA-synthesizing enzyme, glutamic acid decarboxylase in EC were confirmed by immunostaining and immunoblot analysis, respectively. The presence of GABA was further confirmed by immunohistochemistry in the EC lining the human coronary vessel. EC-derived GABA regulated the key mechanisms of ATP synthesis, fatty acid, and pyruvate oxidation in EC. GABA protected EC by inhibiting the reactive oxygen species generation and prevented monocyte adhesion by attenuating vascular cell adhesion molecule -1 and monocyte chemoattractant protein-1 expressions. GABA had no relaxing effect on rat aortic rings. GABA exhibited a dose-dependent fall in blood pressure. However, the fall in BP was abolished after pretreatment with pentolinium.
  
  
  CONCLUSIONS
  Our findings indicate novel potential functions of endothelium-derived GABA.
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.). gchaudhuri@mednet.ucla.edu ssen@mednet.ucla.edu.
authors.forename: Suvajit
authors.initials: S
authors.lastname: Sen
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.).
authors.forename: Sohini
authors.initials: S
authors.lastname: Roy
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.).
authors.forename: Gautam
authors.initials: G
authors.lastname: Bandyopadhyay
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.).
authors.forename: Bari
authors.initials: B
authors.lastname: Scott
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.).
authors.forename: Daliao
authors.initials: D
authors.lastname: Xiao
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.).
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Ramadoss
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.).
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.affiliation: From the Department of Obstetrics and Gynecology (S.S., S.R., B.S., S.R., G.C.) and Department of Molecular and Medical Pharmacology (G.C.) David Geffen School of Medicine at University of California at Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA (S.S., G.C.); Department of Medicine, University of California San Diego, VA San Diego Health Care System (G.B., S.K.M.); and Division of Pharmacology, Department of Basic Sciences, Center for Perinatal Biology, Loma Linda University School of Medicine, CA (D.X.). gchaudhuri@mednet.ucla.edu ssen@mednet.ucla.edu.
authors.forename: Gautam
authors.initials: G
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: adenosine triphosphate; endothelial cell; fatty acids; gamma-aminobutyric acid; pyruvate