30 research outputs found
A second pathway of activation of the Torpedo acetylcholine receptor channel
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine (D-eserine)
with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligandinduced
ion flux into nAChR-rich membrane vesicles and of equilibrium binding. We find that (—)physostigmine
induces cation flux (and also binds to the receptor) even in the presence of saturating concentrations of antagonists
of acetylcholine, such as D-tubocurarine, a-bungarotoxin or antibody WF6, The direct action on the acetylcholine
receptor is not affected by removal of the methylcarbamate function from the drug and thus is not due to
carbamylation of the receptor. Antibodies FKl and benzoquinonium antagonize channel activation (and binding)
of eserine, suggesting that the eserine binding site(s) is separate from, but adjacent to, the acetylcholine binding
site at the receptor. In addition to the channel activating site(s) with an affinity of binding in the 50 nM range,
there exists a further class of low-affinity (K^ ~ mM) sites from which eserine acts as a direct blocker of the
acetylcholine-activatcd channel. Our results suggest the existence of a second pathway of activation of the nAChR
channel
Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel
The reversible acctylchollne esternse inhibitor (-}.physostiilmine (¢serine) is th© prolotypc of a new class of nie~tinlc ucetylcholinc receptor
(nAChR) activating liga,ds: it induces cation fluxes into nAChR.rich membrane vesicl~s from 7~r#eda marmoeata cle~:tric tissue even under condl.
lions of antalionist blocked :tcctylcholin~ binding sil~s (Okonjo, Kuhlm~mn. Maelicke. Neuron, in press). This su~tlest's that escrine exerts it~ than.
nel.activating proi'~rty via binding sites at the nAChR separate from those of tile natural transmitter. We now report thllt eserine e'-m activate
the channel wen when the receptor has t~en preincub~ttcd (des©nsitiz©d) with elevated concentrations of acetylcholi~e, Titus the confornudional
state Of the receptor corresponding to de~nsitixation is confined to the transmitter bindinB rclli0n, leaving the ch=tr'4nel fully activatable ,- albeit
only from other than the tr~msmitter bindin~ site(s)
The murine nuclear orphan receptor GCNF is expressed in the XY body of primary spermatocytes
AbstractWe have studied the expression of the nuclear orphan receptor GCNF (germ cell nuclear factor) on the mRNA and protein level in pubertal and adult mouse testes. We show by Northern and Western blot analyses and by in situ hybridization that GCNF is expressed in spermatocytes and round spermatids of adult mouse testis suggesting that GCNF may be a transcriptional regulator of spermatogenesis. Since the GCNF protein is accumulated in the XY body of late pachytene spermatocytes, it may be involved in transcriptional inactivation of sex chromosomes
Allosteric interactions between distinct structural domains at the nicotinic acetylcholine receptor
Ligand binding to the membrane-bound acetylcholine receptor from Torpedo marmorata: a complete mathematical analysis
Klinische Bedeutung - Dualer Wirkmechanismus von Galantamin zur Behandlung der Alzheimer-Demenz
Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
The plant alkaloid galantamine is an established symptomatic drug treatment for Alzheimer’s disease (AD), providing temporary cognitive and global relief in human patients. In this study, the 5X Familial Alzheimer’s Disease (5XFAD) mouse model was used to investigate the effect of chronic galantamine treatment on behavior and amyloid β (Aβ) plaque deposition in the mouse brain. Quantification of plaques in untreated 5XFAD mice showed a gender specific phenotype; the plaque density increased steadily reaching saturation in males after 10 months of age, whereas in females the density further increased until after 14 months of age. Moreover, females consistently displayed a higher plaque density in comparison to males of the same age. Chronic oral treatment with galantamine resulted in improved performance in behavioral tests, such as open field and light-dark avoidance, already at mildly affected stages compared to untreated controls. Treated animals of both sexes showed significantly lower plaque density in the brain, i.e., the entorhinal cortex and hippocampus, gliosis being always positively correlated to plaque load. A high dose treatment with a daily uptake of 26 mg/kg body weight was tolerated well and produced significantly larger positive effects than a lower dose treatment (14 mg/kg body weight) in terms of plaque density and behavior. These results strongly support that galantamine, in addition to improving cognitive and behavioral symptoms in AD, may have disease-modifying and neuroprotective properties, as is indicated by delayed Aβ plaque formation and reduced gliosis