title: Age-related loss of responsiveness to 2,5-dimethoxy-4-iodoamphetamine in liver sinusoidal endothelial cells.
abstract: Age-related pseudocapillarization of the liver sinusoidal endothelium is associated with impaired lipid and drug metabolism and the development of disease. 2,5-Dimethoxy-4-iodoamphetamine is a serotonin receptor 2 agonist that has been shown to have beneficial effects on the liver sinusoidal endothelium in the setting of partial hepatectomy. Here, we have assessed whether 2,5-dimethoxy-4-iodoamphetamine influences ultrastructure of the sinusoidal endothelium in normal 7- and 24-month-old C57Bl6 mice. Following 48 hours of 2,5-dimethoxy-4-iodoamphetamine administration, we found that the liver endothelium in the young, but not in the old, mice had increased porosity compared with controls. This effect appeared to be modulated by increased fenestration size rather than a change in fenestration number. 2,5-Dimethoxy-4-iodoamphetamine is a useful manipulator of fenestration size in the young liver and could be harnessed in the search for therapeutic interventions for pseudocapillarization.
authors: ANZAC Research Institute, Gate 3 Hospital Road Concord RG Hospital, Concord, NSW 2139, Australia. victoria.cogger@sydney.edu.au.
authors: Victoria C
authors: VC
authors: Cogger
authors: Sarah J
authors: SJ
authors: Mitchell
authors: Alessandra
authors: A
authors: Warren
authors: Rafael
authors: R
authors: de Cabo
authors: David G
authors: DG
authors: Le Couteur
mesh_terms: D000375:Aging / Q000502:physiology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects*; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D000662:Amphetamines; D017366:Serotonin Receptor Agonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 2,5-Dimethoxy-4-iodoamphetamine.; Fenestrations; Liver endothelium
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