448 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 (â)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 (¹serine) 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
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