Increased brain uptake and brain to blood efflux transport of 14C-GABA in spontaneously hypertensive rats

Life Sciences
M Al-AwadiH Al-Sarraf

Abstract

The brain uptake and brain to blood efflux transport of (14)C-GABA were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats using 20 min bilateral in situ brain perfusion in rats anesthetized using urethane. The volume of distribution (Vd) of (14)C-GABA into cerebrospinal fluid (CSF) and brain regions (cortex, diencephalon, cerebellum, and brain stem) was significantly greater in SHR than in the corresponding regions in WKY rats (p<0.05). The estimated Vd value of (14)C-GABA in CSF of SHR was 3.4 fold greater than that in WKY. Also compared to WKY, the Vd of (14)C-GABA into cerebellum and cortex of SHR was 15.3 fold and 19.4 fold greater, respectively. Although the study of blood-brain barrier (BBB) integrity using (3)H-mannitol revealed increased paracellular permeability at the brain capillaries of SHR when compared to WKY rats, this was found to be only partially responsible for the increased (14)C-GABA uptake. The study of brain to blood efflux transport of (14)C-GABA (after loading of brain with (14)C-GABA by vascular perfusion) revealed that the half-time of elimination was significantly shorter in SHR (5.35+/-0.66 min) than in WKY rats (14.83+/-1.94 min), (p<0.001). HPLC analysis rev...Continue Reading

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Citations

Oct 3, 2013·Journal of Cardiovascular Pharmacology·Shuhei KobuchiYasuo Matsumura
Jan 1, 2010·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·K MurphyR H Ettinger
Sep 22, 2009·European Journal of Pharmacology·Shuhei KobuchiYasuo Matsumura
Dec 9, 2014·Clinical and Experimental Pharmacology & Physiology·Shuhei KobuchiKazuhide Ayajiki
Jun 3, 2011·The Journal of Pharmacology and Experimental Therapeutics·Shuhei KobuchiYasuo Matsumura
Aug 28, 2021·Nutrients·Hellen A Oketch-RabahJoseph M Betz

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