Whole-body autoradiographic localization of [3H]phencyclidine and its metabolites in mice.
When evaluated by whole-body autoradiography (WBAR) and quantitative densitometry, [3H]phencyclidine (PCP) equivalents were found to be removed rapidly from blood, after a single iv dose in mice, and avidly taken up as early as 1 min after dosage by glandular tissues including thyroid, salivary glands, pancreas, pituitary and, most prominently, by stomach mucosa. Stomach:blood [3H]PCP concentration ratios showed that rapid secretion of [3H]PCP from mucosa to the stomach contents occurred within 2 min after dosing. During early intervals, chromatographic analysis of tissue sections demonstrated that PCP was present in brain, liver, and gut primarily in its unaltered chemical form. Mice killed at 60 and 120 min showed persistently high levels of [3H]PCP equivalents within the stomach and intestines, these levels being the highest of all other tissues densitometrically measured. The early time course and magnitude of [3H]PCP uptake by stomach glandular mucosa strongly suggests that cycling of PCP occurs principally through gastroenteric recirculation. Very striking was the high concentration of [3H]PCP radioactivity observed within the adrenal as early as 5 min. The concentration of [3H]PCP equivalents in pituitary, choroid plexus, cortex, hippocampus, and thalamus was highest at 1-20 min following injection. Application of high-resolution quantitative WBAR was found to be a useful tool in the study of the biodistribution of labeled PCP, especially during very early post-treatment time points where alternative tissue counting techniques would not be feasible.
Fand
I
I
Department of Psychiatry, State University of New York, Stony Brook 11794.
McNally
W P
WP
Koul
O
O
Yonekura
Y
Y
Som
P
P
Brill
A B
AB
Deutsch
D G
DG
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D010622:Phencyclidine / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014316:Tritium
D014316:Tritium; D010622:Phencyclidine