Perivascular Adipocytes Store Norepinephrine by Vesicular Transport.
adipocytes
adipose tissue
catecholamines
norepinephrine
obesity
Journal
Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1524-4636
Titre abrégé: Arterioscler Thromb Vasc Biol
Pays: United States
ID NLM: 9505803
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
21
12
2018
medline:
4
12
2019
entrez:
21
12
2018
Statut:
ppublish
Résumé
Objective- Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter). Approach and Results- High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202-a functional and fluorescent VMAT probe-in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine. Conclusions- This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension.
Identifiants
pubmed: 30567483
doi: 10.1161/ATVBAHA.118.311720
pmc: PMC6344267
mid: NIHMS1515962
doi:
Substances chimiques
Slc18a1 protein, rat
0
Slc18a2 protein, rat
0
Vesicular Monoamine Transport Proteins
0
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-199Subventions
Organisme : NHLBI NIH HHS
ID : F31 HL128035
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD072968
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM092715
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL143937
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL070687
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007974
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111997
Pays : United States
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