Chronic nicotine exposure in tobacco smokers or experimental animals is shown to result in an increase in receptor amount, indicating that nicotine-induced up-regulation reflects properties of the alpha 4 beta 2 receptor protein, rather than being an adaptive response unique to the neurons in which these receptors are normally expressed.
Overnight treatment with nicotine increased the number of nAChRs and increased the proportion of the (alpha4)(2)(beta2)(3) stoichiometry, raising the possibility for an interesting mode of synaptic regulation for nicotinic signaling in the mammalian brain.
Nicotinic acetylcholine receptors formed from combinations of α3, β2, β4, and α5 subunits are found in chicken ciliary ganglion neurons and some human neuroblastoma cell lines and Nicotine, like the structurally similar toxin epibatidine, distinguishes by binding affinity two subtypes of receptors containing α3 subunits in SH-SY5Y cells.
Overnight treatment with nicotine increased the number of nAChRs and increased the proportion of the (alpha4)(2)(beta2)(3) stoichiometry, raising the possibility for an interesting mode of synaptic regulation for nicotinic signaling in the mammalian brain.
It is demonstrated that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy.
Mice whose α4 nicotinic receptor subunits are replaced by normally functioning fluorescently tagged subunits provide quantitative studies of receptor regulation at micrometer resolution, providing a possible explanation for two effects of chronic nicotine: sensitization of synaptic transmission in forebrain and tolerance of dopaminergic neuron firing in midbrain.
Pathogenic roles of AChRs are being discovered in many diseases involving mechanisms ranging from mutations, to autoimmune responses, to the unknown; involving cell types ranging from muscles, to neurons, to keratinocytes; and involving signs and symptoms ranging from muscle weakness to epilepsy, to neurodegenerative disease, to psychiatric disease, and nicotine addiction.
Prepared concatamers of alpha4 and beta2 subunits for human nicotinic acetylcholine receptors (AChRs) provided insight into the structure and function ofalpha4beta2 AChRs, emphasizing the functional differences between alpha4 beta2 A ChRs of different stoichiometries.
This review will begin with a brief summary of muscle type AChRs because they are the archetype for studies of neuronal nicotinic A ChRs in particular and ligand-gated ion channels in general.
In the present study, three different monoclonal antibodies raised against the α7 subunit were used to map its distribution throughout the central nervous system of the rat.