ArticleProceedings of the National Academy of Sciences of the United States of America1996
Threonine-for-leucine mutation within domain M2 of the neuronal alpha(7) nicotinic receptor converts 5-hydroxytryptamine from antagonist to agonist.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 69 citations in OpenAlex.
- Diversity of Nicotinic Acetylcholine Receptor Positive Allosteric Modulators Revealed by Mutagenesis and a Revised Structural Model.Molecular pharmacology · 2018Article
- Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, CHRM2, and CHRM5: effects of drug and environmental treatments.Journal of neurochemistry · 2017Article
- The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.Neuropharmacology · 2015Article
- Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery.Acta pharmacologica Sinica · 2015Review
- Ginseng ginsenoside pharmacology in the nervous system: involvement in the regulation of ion channels and receptors.Frontiers in physiology · 2014Review
- A single channel mutation alters agonist efficacy at 5-HT3A and 5-HT3AB receptors.British journal of pharmacology · 2013Article
- Discriminating between 5-HT₃A and 5-HT₃AB receptors.British journal of pharmacology · 2013Review
- Structural basis of ligand recognition in 5-HT3 receptors.EMBO reports · 2013Article
- Pore structure of the Cys-loop ligand-gated ion channels.Neurochemical research · 2009Review
- Properties of glutamate receptors of Alzheimer's disease brain transplanted to frog oocytes.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Structural determinants of selective alpha-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Microtransplantation of membranes from cultured cells to Xenopus oocytes: a method to study neurotransmitter receptors embedded in native lipids.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Amyloid beta(1-42) peptide alters the gating of human and mouse alpha-bungarotoxin-sensitive nicotinic receptors.The Journal of physiology · 2003Article
- Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- The single-channel properties of human acetylcholine alpha 7 receptors are altered by fusing alpha 7 to the green fluorescent protein.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Some properties of human neuronal alpha 7 nicotinic acetylcholine receptors fused to the green fluorescent protein.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Evidence for a centrally located gate in the pore of a serotonin-gated ion channel.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A study was made of the effects of 5-hydroxytryptamine (5HT) on homomeric neuronal nicotinic receptors (nAcChoR) expressed in Xenopus oocytes after injection of cDNA encoding the wild-type chicken alpha(7) subunit. Acetylcholine (AcCho) elicited large currents (IAcCho) that were reduced by 5HT in a reversible and dose-dependent manner, with a half-inhibitory concentration (IC50) of 56 microM and a Hill coefficient (nH) of 1.2. The inhibition of IAcCho by 5HT was noncompetitive and voltage independent, a behavior incompatible with a channel blockade mechanism. 5HT alone did not elicit membrane currents in oocytes injected with the wild-type alpha(7) subunit cDNA. In contrast, 5HT elicited membrane currents (I5HT) in oocytes injected with cDNA encoding an alpha(7) mutant subunit with a threonine-for-leucine-247 substitution (L247T alpha(7)). I5HT was inhibited by the potent nicotinic receptor blockers alpha-bungarotoxin (100 nM) and methyllycaconitine (1 microM). Furthermore, the characteristics of I5HT, including its voltage dependence, were similar to those of IAcCho. The 5HT dose-I5HT response gave an apparent dissociation constant EC50 of 23.5 microM and a Hill coefficient nH of 1.7, which were not modified by the presence of AcCho. Similarly, the apparent affinity of L247T alpha(7) for AcCho as well as its cooperativity were not influenced by 5HT, indicating a lack of mutual interactions between 5HT and AcCho. These results show that 5HT is a potent noncompetitive antagonist of neuronal alpha(7) nAcChoR, but it becomes a noncompetitive agonist following mutation of the highly conserved leucine residue 247 located in the channel domain M2.
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