Microarray and Proteomics Analysis on Neurotransmitter ( Nicotinic Acetylcholine Cys Loop Receptor ) By using Bioinformatics Tools

Excessive inflammation and tumor-necrosis factor (TNF) synthesis causes morbidity and mortality in diverse human diseases including endotoxaemia, sepisis, rheumatoid arthritis and inflammatory bowel diseases. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate responses and prevent excessive inflammation. The release of system, through the vagus nerve, can inhibit significantly and rapidly the release of macrophage TNF, and attenuate systemic inflammatory responses. This physiological mechanism, termed the ‘cholinergic anti-inflammatory pathway’ has major implications in immunology and in therapeutics; however, the identity of the essential macrophage acetylcholine mediated (cholinergic) receptor that responds to vagus nerve signals was previously unknown. Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ligand-gated ion channels in cells' plasma membranes. Like the other type of acetylcholine receptors, muscarinic acetylcholine receptors (mAChRs), their opening is triggered by the neurotransmitter acetylcholine (ACh), but they are also opened by nicotine. Also in contrast to muscarinic ACh receptors, nicotinic acetylcholine cys loop receptors do not operate with a second messenger, but open themselves forming an ion channel. Their action is inhibited by curare. Nicotinic acetylcholine receptors are present in many tissues in the body. The neuronal receptors are found in the central nervous system and the peripheral nervous system. The neuromuscular receptors are found in the neuromuscular junctions of somatic muscles; stimulation of these receptors causes muscular contraction. Here we report that the nicotinic acetylcholine receptor alpha-7 subunit is required for acetylcholine inhibition of macrophage TNF release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in widetype mice, but fails to inhibit TNF synthesis in 7 deficient cytokine syntheses by the cholinergic anti-inflammation pathway. Modeller 9v2 was used to design the receptor nicotinic acetylcholine receptor alpha-7 subunit. Genemaths XT was used for microarray analysis of the receptor. Molecular docking of nicotinic acetylcholine cys loop receptor (alpha-7 subunit) with the ligand 1sq3 by Autodock 4.0 to obtain biomolecules for the control of neural diseases. [Sabitri Nahak, Gayatri Nahak and Rajani Kanta Sahu. Microarray and Proteomics Analysis on Neurotransmitter (Nicotinic Acetylcholine Cys Loop Receptor) by using Bioinformatics Tools. Researcher. 2011;3(3):27-33]. (ISSN: 1553-9865). http://www.sciencepub.net. Key word: nAChR (alpha-7subunit), Molecular modeling, Neurotransmitter, Microarray, Docking, 1sq3, Ligand.