A7DB: a relational database for mutational, physiological and pharmacological data related to the α7 nicotinic acetylcholine receptor

BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) are pentameric proteins that are important drug targets for a variety of diseases including Alzheimer's, schizophrenia and various forms of epilepsy. One of the most intensively studied nAChR subunits in recent years has been α7. This subunit can form functional homomeric pentamers (α7)(5), which can make interpretation of physiological and structural data much simpler. The growing amount of structural, pharmacological and physiological data for these receptors indicates the need for a dedicated and accurate database to provide a means to access this information in a coherent manner. DESCRIPTION: A7DB is a new relational database of manually curated experimental physiological data associated with the α7 nAChR. It aims to store as much of the pharmacology, physiology and structural data pertaining to the α7 nAChR. The data is accessed via web interface that allows a user to search the data in multiple ways: 1) a simple text query 2) an incremental query builder 3) an interactive query builder and 4) a file-based uploadable query. It currently holds more than 460 separately reported experiments on over 85 mutations. CONCLUSIONS: A7DB will be a useful tool to molecular biologists and bioinformaticians not only working on the α7 receptor family of proteins but also in the more general context of nicotinic receptor modelling. Furthermore it sets a precedent for expansion with the inclusion of all nicotinic receptor families and eventually all cys-loop receptor families

The actions of B-Amyloid and related peptides on Neuronal Nicotinic Acetylcholine receptors

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A7DB: A relational database for mutational, physiological and pharmacological data related to the alpha7 nicotinic acetylcholine receptor

Background Nicotinic acetylcholine receptors (nAChRs) are pentameric proteins that are important drug targets for a variety of diseases including Alzheimer’s, schizophrenia and various forms of epilepsy. One of the most intensively studied nAChR subunits in recent years has been a7. This subunit can form functional homomeric pentamers (a7)5, which can make interpretation of physiological and structural data much simpler. The growing amount of structural, pharmacological and physiological data for these receptors indicates the need for a dedicated and accurate database to provide a means to access this information in a coherent manner. Description A7DB http://www.lgics.org/a7db/ is a new relational database of manually curated experimental physiological data associated with the a7 nAChR. It aims to store as much of the pharmacology, physiology and structural data pertaining to the a7 nAChR. The data is accessed via web interface that allows a user to search the data in multiple ways: 1) a simple text query 2) an incremental query builder 3) an interactive query builder and 4) a file-based uploadable query. It currently holds more than 460 separately reported experiments on over 85 mutations. Conclusions A7DB will be a useful tool to molecular biologists and bioinformaticians not only working on the a7 receptor family of proteins but also in the more general context of nicotinic receptor modelling. Furthermore it sets a precedent for expansion with the inclusion of all nicotinic receptor families and eventually all cys-loop receptor families

Subtype-specific actions of β-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (α7, α4β2, α3β4) expressed in Xenopus laevis oocytes

1. Two-electrode voltage-clamp electrophysiology has been used to study the actions of two amyloid peptides (Aβ(1–42), Aβ(1–40)) on α7, α4β2 and α3β4 recombinant human neuronal nicotinic acetylcholine receptors (nicotinic AChRs), heterologously expressed in Xenopus laevis oocytes. 2. The application of Aβ(1–42) or Aβ(1–40) (1 pM–100 nM) for 5 s does not directly activate expressed human α7, α4β2 or α3β4 nicotinic AChRs. 3. Aβ(1–42) and Aβ(1–40) are antagonists of α7 nicotinic AChRs. For example, 10 nM Aβ(1–42) and Aβ(1–40) both reduced the peak amplitude of currents recorded (3 mM ACh) to 48±5 and 45±10% (respectively) of control currents recorded in the absence of peptide. In both the cases the effect is sustained throughout a 30 min peptide application and is poorly reversible. 4. Aβ(1–42) and Aβ(1–40) (10 nM) enhance currents recorded in response to ACh (3 mM) from oocytes expressing α4β2 nicotinic AChRs by 195±40 and 195±41% respectively. This effect is transient, reaching a peak after 3 min and returning to control values after a 24 min application of 10 nM Aβ(1–42). We observe an enhancement of 157±22% of control ACh-evoked current amplitude in response to 100 nM Aβ(1–42) recorded from oocytes expressing α4β2 nicotinic AChRs. 5. Aβ(1–42) and Aβ(1–40) (10 nM) were without antagonist actions on the responses of α3β4 nicotinic AChRs to ACh (1 nM–3 mM)