Home About us Contact
|
Home About us Contact | ||
|
|
||
Nicotinic Acetylcholine Receptor Subunits (nicotinic + acetylcholine_receptor_subunit)
Selected AbstractsNicotinic ,5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbersJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Robert W. B. Brown Abstract Neuronal nicotinic acetylcholine receptor subunit ,5 mRNA is widely expressed in the CNS. An ,5 gene polymorphism has been implicated in behavioral differences between mouse strains, and ,5-null mutation induces profound changes in mouse acute responses to nicotine. In this study, we have examined the distribution and prevalence of ,5* nicotinic acetylcholine receptor in mouse brain, and quantified the effects of ,5-null mutation on pre-synaptic nicotinic acetylcholine receptor function (measured using synaptosomal 86Rb+ efflux) and overall [125I]epibatidine binding site expression. ,5* nicotinic acetylcholine receptor expression was found in nine of fifteen regions examined, although < 20% of the total nicotinic acetylcholine receptor population in any region contained ,5. Deletion of the ,5 subunit gene resulted in localized loss of function (thalamus, striatum), which was itself confined to the DH,E-sensitive receptor population. No changes in receptor expression were seen. Consequently, functional changes must occur as a result of altered function per unit of receptor. The selective depletion of high agonist activation affinity sites results in overall nicotinic function being reduced, and increases the overall agonist activation affinity. Together, these results describe the receptor-level changes underlying altered behavioral responses to nicotine in nicotinic acetylcholine receptor ,5 subunit-null mutants. [source] Association of idiopathic generalized epilepsy with polymorphisms in the neuronal nicotinic acetylcholine receptor subunitsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2007Cheng-Chun Lee Abstract Idiopathic generalized epilepsy (IGE) refers to a common group of epilepsies, and genetic factors play an important role in the pathogenesis of these disorders. Mutations in CHRNA4 and CHRNB2 are associated with some cases of familial epilepsies classified as autosomal-dominant nocturnal frontal lobe epilepsies. We aimed to evaluate whether polymorphisms of CHRNA4 and CHRNB2are associated with IGE. A total of 75 children with IGE and 80 normal control subjects were included in the study. Each genetic polymorphism was typed by polymerase chain reaction (PCR)-based restriction analysis. The genotypes and allelic frequencies of each polymorphism were compared between the IGE patients and controls. The results showed that genotype and allelic frequency for CHRNB2 did not differ significantly between the groups. However, the genotype proportion of the CHRNA4 (Ser543Ser) gene in both groups was significantly different (P<0.0001). The T allele frequency was significantly higher (P=0.0126) in patients with IGE compared to healthy controls. The odds ratio (OR) for developing IGE in individuals with the CHRNA4 (Ser543Ser)-T homozygote was 4.9 (95% confidence interval (CI), 1.71,14.04) compared to individuals with two copies of the CHRNA4 (Ser543Ser)-C allele. This study demonstrates that the CHRNA4 gene may be one of the susceptibility factors for IGE. J. Clin. Lab. Anal. 21:67,70, 2007. © 2007 Wiley-Liss, Inc. [source] Nicotinic acetylcholine receptor structure and function in the efferent auditory systemTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2006Lawrence R. Lustig Abstract This article reviews and presents new data regarding the nicotinic acetylcholine receptor subunits ,9 and ,10. Although phylogentically ancient, these subunits have only recently been identified as critical components of the efferent auditory system and medial olivocochlear pathway. This pathway is important in auditory processing by modulating outer hair cell function to broadly tune the cochlea and improve signal detection in noise. Pharmacologic properties of the functionally expressed ,9,10 receptor closely resemble the cholinergic response of outer hair cells. Molecular, immunohistochemical, and knockout mice studies have added further weight to the role this receptor plays in mediating the efferent auditory response. Alternate and complementary mechanisms of outer hair cell efferent activity might also be mediated through the nAChR ,9,10, either through secondary calcium stores, second messengers, or direct protein-protein interactions. We investigated protein-protein interactions using a yeast-two-hybrid screen of the nAChR ,10 intracellular loop against a rat cochlear cDNA library. Among the identified proteins was prosaposin, a precursor of saposins, which have been shown to act as neurotrophic factors in culture, can bind to a putative G0-coupled cell surface receptor, and may be involved in the prevention of cell death. This study and review suggest that nAChR ,9,10 may represent a potential therapeutic target for a variety of ear disorders, including preventing or treating noise-induced hearing loss, or such debilitating disorders as vertigo or tinnitus. Anat Rec Part A, 2006. © 2006 Wiley-Liss, Inc. [source] Molecular characterization of two nicotinic acetylcholine receptor subunits from Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae)ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2009Pei-An Tang Abstract Two nicotinic acetylcholine receptor (nAChR) subunit genes, Lb,1 and Lb,8, were isolated and characterized from psocid, Liposcelis bostrychophila Badonnel, using the rapid amplification of cDNA ends (RACE) technique. They are the first two nAChR family members isolated from the insect order of Psocoptera. The full-length cDNAs of Lb,1 (GenBank accession number: EU871527) and Lb,8 (EU871526) consist of 2,025 and 1,763 nucleotides, respectively, and an open reading frame of 1,644 and 1,608,bp encoding 547 and 535 amino acid proteins, respectively. Both genes have typical features of nAChR family members, though they share only 56% identity in amino acid sequence. The dendrogram generated by the MEGA 3.1 program shows that the protein deduced by Lb,1 had the closest phylogenetic relationship to Agam,1 from Anopheles gambiae and Amel,1 from Apis mellifera, and Lb,8 shares the highest identity with Agam,8 from An. gambiae and Amel,8 from A. mellifera. Quantitative real-time PCR analysis showed that Lb,1 was expressed 2.03,6.54-fold higher than Lb,8 at the different developmental stages of L. bostrychophila. The highest expression levels of Lb,1 and Lb,8 were both detected at adult stage and the lowest were at the third and fourth nymphal stages, respectively. There was a stable and relatively low expression level for Lb,1, whereas there was a descending expression pattern for Lb,8 in the 1st through the 4th nymphal stadia. © 2009 Wiley Periodicals Inc. [source] | ||||||||||