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This study characterized the pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, its metabolite, ADL 08-0011, and methylnaltrexone. The activities of the compounds were investigated with respect to human or guinea pig opioid receptor binding and function in recombinant cell lines and mechanical responsiveness of the guinea(More)
Glutamate binding to the N-methyl-D-aspartic acid (NMDA) receptor decreases in two strains of aged mice. In BALB/c mice the Bmax values decline 16% by 10 months and 45% by 30 months of age when compared to 3 months. The Kd increased more by 10 months (+29%) than by 30 months (+14%). In the C57Bl strain the Bmax was unaltered by 10 months but decreased 17%(More)
Many aspects of calcium homeostasis change with aging. Numerous calcium compartments complicate studies of altered calcium regulation. However, age-related decreases in calcium permeation across membranes and mobilization from organelles may be a common fundamental change. Deficits in ion movements appear to lead to altered coupling of calcium-dependent(More)
Excitatory amino acids have been implicated in the pathogenesis of hepatic encephalopathy. In the present study, kainate, quisqualate and N-methyl-D-aspartate (NMDA) subclasses of L-glutamate receptors were measured in adult rat brain by quantitative receptor autoradiography following surgical construction of an end-to-side portacaval anastomosis (PCA). PCA(More)
Acetylcholine (ACh) synthesis in vivo is known to decrease during the aging process (senescence). To elucidate the molecular mechanism(s) of this age-related decline, we studied brain slices from 3-, 10-, and 30-month-old mice of two strains (C57B1 and Balb/c). In low K+ media, oxidative metabolism as measured by 14CO2 production decreased with aging from(More)
Immature hippocampal neurons (E-18) were maintained in defined medium for up to 3 weeks and their susceptibility to N-methyl-D-aspartic acid (NMDA)-induced cell death was studied at various days in vitro. Upon acute exposure to NMDA (5 min), hippocampal neurons in vitro (8-12 days after plating) showed cell body swelling and dendritic degeneration that(More)
  • C Peterson
  • 1992
Alterations in calcium transport appear to be functionally significant. Treatment with drugs that promote calcium uptake partially reverse some of the age-related deficits in calcium-dependent processes. Thus, the relevance of decreased calcium coupled receptor binding is supported by the ability of 3,4-diaminopyridine to promote acetylcholine release by(More)
A purified polyclonal antibody preparation was made against recombinant brain-derived neurotrophic factor (BDNF) in guinea pig and characterized for use in immunoassays and immunohistochemistry. The anti-BDNF antibodies specifically recognized BDNF in Western blots and immunoprecipitation. There was no cross-reactivity with the other known mammalian members(More)
Previous studies suggest that alterations of brain glutamate synthesis and release occur in experimental thiamine deficiency. In order to assess the integrity of post-synaptic glutamatergic receptors in thiamine deficiency, binding sites for [3H]glutamate (displaced by NMDA), [3H]-kainate, and [3H]quisqualate (AMPA sites) were evaluated using Quantitative(More)
To test the hypothesis that decreased acetylcholine (ACh) metabolism during hypoxia is behaviorally important, the effects of cholinergic drugs and 4-aminopyridine, an enhancer of ACh release, were examined in hypoxic mice. Chemical hypoxia (150 mg/kg NaNO2) reduced tight rope test scores from 13.2 +/- 0.2 to 2.8 +/- 0.3. 4-Aminopyridine partially reversed(More)