{'fraction_non_alphanumeric': 0.04929942916450441, 'fraction_numerical': 0.014530358069538143, 'mean_word_length': 4.704142011834319, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Transport of digoxin into brain microvessels and choroid plexuses isolated from guinea pig.

To characterize the efflux system of digoxin, a cardiac glycoside, from the brain to the blood through the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, the accumulation of digoxin by the brain microvessel or the choroid plexus isolated from guinea pig brain was investigated. The accumulation of digoxin by the brain microvessel has a saturable component (Km = 0.163 microM, Vmax = 0.142 nmol/mL of tissue/min), with a nonsaturable component [Kd = 0.203 cell-to-medium (C:M) ratio/min] that was decreased by hypothermia (Q10 = 2.9), sulfhydryl reagent, and quinidine, but not by a metabolic inhibitor [2,4-dinitrophenol (DNP)]. It was concentration- and Na+-dependent. The accumulation of digoxin by the choroid plexus was also saturable (Km = 1.9 microM, Vmax = 3.8 nmol/mL of tissue/min), and was decreased by hypothermia (Q10 = 4.4), sulfhydryl reagents, ouabain, and quinidine, but not by metabolic inhibitors (DNP, KCN); it was also concentration- and Na+-dependent. The binding of digoxin to the homogenate of choroid plexus was one-tenth of digoxin accumulation by the intact choroid plexus, suggesting that digoxin is transported into the cells and bound to the cytosol fraction. The value of (Vmax/Km + Kd) multiplied by the total tissue weight of the microvessel per guinea pig is approximately 10-fold that of Vmax/Km multiplied by the tissue weight of the choroid plexus, although (Vmax/Km + Kd) per milliliter of the microvessel is half the Vmax/Km value of the choroid plexus. These findings suggest that digoxin can be excreted from both the brain and the cerebrospinal fluid to blood by a carrier-mediated diffusion system which is inhibited by quinidine, and that a main route of digoxin efflux from the brain to the blood is not through the blood-CSF barrier, but through the blood-brain barrier.