Ligands, receptor models, and evolution.
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Animals↗
Biomedical subjects
G Lunt
Publications and source records attributed to G Lunt.
Nicotinic acetylcholine receptors in cultured neurons from the hippocampus and brain stem of the rat characterized by single channel recording.
Single channel recording techniques have been applied to neurons cultured from the hippocampus and the respiratory area of the brain stem of fetal rats in order to search for nicotinic acetylcholine receptors (nAChR) in the central nervous system. In addition to acetylcholine (ACh), the potent and specific agonist (+)-anatoxin-a was also used to characterize nicotinic channels. nAChRs were concentrated on the somal surface near the base of the apical dendrite, and in some patches their density was sufficient to record 2 or more channel openings simultaneously. Although a multiplicity of conductance states was also evident, the predominant population showed a single channel conductance of 20 pS at 10 degrees C. Thus, these neuronal nAChRs resembled the embryonic or denervated-type nAChRs in muscle. However, channel opening and closing kinetics were faster than reported for similar conductance channels in muscle. Therefore the nicotinic channels described here are similar but not identical to those of the well-characterized muscle nAChR, in agreement with biochemical, pharmacological, and molecular genetic studies on brain AChR.
Animals↗
Stimulation by mitogens and neuronal membranes of lymphocytes from patients with motor neurone disease.
Stimulation of lymphocytes from motor neurone disease patients by either concanavalin A or PHA was shown to be significantly depressed relative to that from normal controls, as assayed by incorporation of [3H]thymidine or [3H]leucine or by glucose uptake. Corresponding significant differences were not shown by assays based upon incorporation of [3H]uridine or of lactate release. Lymphocytes from 4 out of 14 motor neurone disease patients showed a blastogenic response to membranes from rat spinal cord cells, compared with those from 0 out of 9 normal controls. These results not only suggest the possibility of an impaired cellular immune control in MND patients but also indicate the presence of lymphocytes sensitised specifically to neuronal membrane components.
Adult↗
gamma-Aminobutyric acid receptor complex of insect CNS: characterization of a benzodiazepine binding site.
The specific binding of [N-methyl-3H]flunitrazepam ([3H]FNZP) to a membrane fraction from the supraoesophageal ganglion of the locust (Schistocerca gregaria) has been measured. The ligand binds reversibly with a KD of 47 nM. The binding is Ca2+-dependent, a property not found for the equivalent binding site in vertebrate brain. The pharmacological characteristics of the locust binding site show similarities to both central and peripheral benzodiazepine receptors in mammals. Thus binding is enhanced by gamma-aminobutyric acid (GABA), a feature of mammalian central receptors, whereas the ligand Ro 5-4864 was more effective in displacing [3H]FNZP than was clonazepam, which is the pattern seen in mammalian peripheral receptors. The locust benzodiazepine binding site was photoaffinity-labelled by [3H]FNZP, and two major proteins of Mr 45K and 59K were specifically labelled. In parallel experiments with rat brain membranes a single major protein of Mr 49K was labelled, a finding in keeping with many reports in the literature. We suggest that the FNZP binding site described here is part of the GABA receptor complex of locust ganglia. The insect receptor appears to have the same general organization as its mammalian counterpart but differs significantly in its detailed properties.
Affinity Labels↗
Interaction of foetal and adult human acetylcholine receptors with serum from patients with myasthenia gravis.
Acetylcholine receptors were partially purified from foetal and adult human muscle and their binding to myasthenic serum was compared. No significant differences between the binding characteristics of the two receptor types were detected; indicating the absence, at least in 14-22-week-old foetuses of antigenic sites unique to foetal receptor and recognised by myasthenic sera.
Adult↗
Immunological cross-reactivity between the alpha-bungarotoxin-binding component from rat brain and nicotinic acetylcholine receptor.
An alpha-bungarotoxin-binding protein was partially purified from rat brain and, when complexed with [125I] alpha-bungarotoxin, was shown to behave as a single radiolabelled protein that is distinct from the similarly complexed nAChR from Torpedo marmorata. The alpha-bungarotoxin-binding protein was used as antigen in radioimmunoassays for rabbit anti-(rat muscle nAChR) and rabbit anti-(Torpedo nAChR) antibodies, giving titres approximately 5% and 0.5%, respectively, of those obtained by using homologous antigen in the same assay.
Animals↗