Background: In rodents, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inactive 11-dehydrocorticosterone (DHC) into active corticosterone. The mRNA and activity of 11beta-HSD1 have been shown to be present in batch-incubated pancreatic islets from the ob/ob mouse. In other tissues, 11beta-HSD1 expression has been demonstrated to be regulated by glucocorticoids.
View Article and Find Full Text PDFThe influence of beta-amyloid on cholinergic neurotransmission was studied by measuring alterations in nicotinic acetylcholine receptors (nAChRs) in autopsy brain tissue from subjects carrying the Swedish amyloid precursor protein (APP) 670/671 mutation. Significant reductions in numbers of nAChRs were observed in various cortical regions of the Swedish 670/671 APP mutation family subjects (-73 to -87%) as well as in sporadic Alzheimer's disease (AD) cases (-37 to -57%) using the nicotinic agonists [3H]epibatidine and [3H]nicotine, which bind with high affinity to both alpha3 and alpha4 and to alpha4 nAChR subtypes, respectively. Saturation binding studies with [3H]epibatidine revealed two binding sites in the parietal cortex of AD subjects and controls.
View Article and Find Full Text PDFEpibatidine, a potent nicotinic agonist, was used to study the regional distribution of nicotinic acetylcholine receptor binding sites in the human brain. Saturation studies performed in the human temporal cortex with (+/-)-[3H]epibatidine revealed binding to two binding sites with Kd and Bmax values of 0.018 and 4.
View Article and Find Full Text PDFThe present study further investigated whether nicotinic acetylcholine receptor (nAChR) subtypes differ in their ability to up-regulate following chronic exposure to nicotinic agonists. Seven nicotinic agonists were studied for their ability to influence the number of chick alpha4beta2 nAChR binding sites stably transfected in fibroblasts (M10 cells) following 3 days of exposure. The result showed a positive correlation between the Ki values for binding inhibition and EC50 values for agonist-induced alpha4beta2 nAChR up-regulation.
View Article and Find Full Text PDFThe number of nicotinic and muscarinic receptors and choline acetyltransferase (ChAT) activity were investigated in the temporal cortex of patients with Alzheimer's disease (AD) with different apolipoprotein E (APOE) genotypes. A significant reduction in the ChAT activity (P < 0.001) and in the number of nicotinic receptors (P < 0.
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