Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anabaseine is a naturally occurring toxin that stimulates a variety of neuronal and muscle nicotinic receptors. GTS-21 [3-(2,4-dimethoxybenzylidene)anabaseine], an anabaseine derivative, selectively stimulates alpha 7-containing nicotinic receptors. Here we report the first in vivo study of the effects of these two nicotinic agonists on cortical extracellular acetylcholine (ACh), dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels, measured with a microdialysis probe placed within the frontoparietal cortex in the absence of a cholinesterase inhibitor. At 3.6 mumol/kg, s.c., anabaseine increased cortical ACh and NE above baseline values without significantly affecting DA and 5-HT. The ACh and NE elevations were inhibited by i.p. pre-administration (4.9 mumol/kg) of the nicotinic antagonist mecamylamine (Mec). In contrast, GTS-21 (3.6 mumol/kg, s.c.) significantly increased NE and DA without affecting ACh and 5-HT levels. Following Mec injection, GTS-21 increased ACh 25-fold and 5-HT 13-fold, while NE and DA levels were slightly decreased in comparison with GTS-21 alone. We suggest that at the dose used, Mec may preferentially block high affinity nicotinic receptors which normally provide an inhibitory influence upon ACh release, thereby permitting expression of the complete stimulatory effect of GTS-21 on neuronal alpha 7-receptors. GTS-21 and other receptor subtype-selective nicotinic agonists should be helpful in clarifying the roles of particular nicotinic receptors in modulating cortical neurotransmitter levels.
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PMID:Nicotinic agonist modulation of neurotransmitter levels in the rat frontoparietal cortex. 924 21

We have established a chronic cerebral hypoperfusion model that is produced by permanent occlusion of bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus 1-3 days after 2VO and infarctions in the striatum 7 days after 2VO. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2). Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after 2VO. Marked increase in GFAP staining in astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. In the 8-arm radial maze performance, the 2VO rats showed a higher rate of errors than the sham-operated control during repeated training periods. THA (9-amino-1,2,3,4-tetrahydroacridine), a cholinesterase inhibitor and GTS-21 (3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride), a central nicotinic acetylcholine-receptor agonist improved the learning impairment in the radical maze task of 2VO rats. GTS-21 administration exerted a protective effect against the neuropathological changes that followed 2VO. Taken together, the 2VO rat appears to be a useful model for investigating the pathophysiology of human dementia and to elucidate the therapeutic potential of drugs for this disease.
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PMID:[Availability of 2VO rats as a model for chronic cerebrovascular disease]. 1020 83