Acetylcholine distribution

Conversely, in a membrane model, acetylcholine showed mean log P values very similar to those exhibited in water. This was due to the compound remaining in the vicinity of the polar phospholipid heads, but the disappearance of extended forms decreased the average log P value somewhat. This suggests that an anisotropic environment can heavily modify the conformational profile of a solute, thus selecting the conformational clusters more suitable for optimal interactions. In other words, isotropic media select the conformers, whereas anisotropic media select the conformational clusters. The difference in conformational behavior in isotropic versus anisotropic environments can be explained considering that the physicochemical effects induced by an isotropic medium are homogeneously uniform around the solute so that all conformers are equally influenced by them. In contrast, the physicochemical effects induced by an anisotropic medium are not homogeneously distributed and only some conformational clusters can adapt to them. 

The development of antibodies against ChAT allowed the distribution of neurons producing acetylcholine in the nervous system to be revealed (Mesulam et al., 1983 Armstrong et al., 1983 Jones Beaudet, 1987 Vincent Reiner, 1987). In the context of control of wakefulness and REM sleep two groups of cholinergic neurons are of primary importance. Neurons located in the basal forebrain and medial septum provide the cholinergic innervation of the cerebral... 

Jones, B. E. Beaudet, A. (1987). Distribution of acetylcholine and catecholamine neurons in the cat brainstem a choline acetyltransferase and tyrosine hydroxylase immunohistochemical study. J. Comp. Neurol. 261, 15-32. 

Wooltorton, J.R., Pidoplichko, V.I., Broide, R.S., Dani, J. A. Differential desensitization and distribution of nicotinic acetylcholine receptor subtypes in midbrain dopamine areas. J. Neurosci. 23 3176, 2003. 

Harkness, P., Millar, N. Changes in conformation and subcellular distribution of a4b2 nicotinic acetylcholine receptors revealed by chronic nicotine treatment and expression of subunit chimeras. J. Neurosci. 22 10172, 2002. 

LaRochelle, W.J., and Froehner, S.C. (1986a) Determination of the tissue distributions and relative concentrations of the postsynaptic 43-kDa protein and the acetylcholine receptor in Torpedo. J. Biol. Chem. 261, 5270-5274. 

Neurotransmission in autonomic ganglia is more complex than depolarization mediated by a single transmitter 190 Muscarinic receptors are widely distributed at postsynaptic parasympathetic effector sites 190 Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber 191 Competitive blocking agents cause muscle paralysis by preventing access of acetylcholine to its binding site on the receptor 191... 

Weinberger, D. R., Gibson, R., Coppola, R. et al. The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography. Arch. Neurol. 48 169-176,1991. 

Elgoyhen AB, Vetter DE, Katz E, RotWinCV, Heinemann SF, Boulter J (2001) alO a determinant of nicotinic cholinergic receptor function in mammalian vestibular and chochlear mechanosen-sory hair cells. Proc Natl Acad Sci 98 3501-3506 Fabian-Fine R, Skehel P, Erington ML, Davies HA, Sher E, Stewart MG, Fine A (2001) Ultra-structural distribution of the a7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci 21 7993-8003... 

Severance EG, Cuevas J (2004) Distribution and synaptic localization of nicotinic acetylcholine receptors containing a novel alpha7 subunit isoform in embryonic rat cortical neurons. Neurosci Lett 372 104-109... 

Inhaled nicotine is efficiently delivered to the brain (see chapter by Benowitz, this volume) where it selectively interacts with its central targets, the neuronal nicotinic acetylcholine receptors (nAChRs). The multiple subtypes of uAChR (see chapter by Collins et al, this volume) all bind nicotine but with different affinities, depending on the subunit composition of the uAChR. Binding may result in activation or desensitisation of uAChRs, reflecting the temporal characteristics of nicotine dehvery and local concentration of nicotine. Another level of complexity of the actions of nicotine reflects the widespread and non-uniform distribution of uAChR subtypes within the brain, such that nicotine can influence many centrally regulated functions in addition to the reward systems. In this chapter, we address the consequences of nicotine interactions with nAChRs at the molecular, cellular and anatomical levels. We critically evaluate experimental approaches, with respect to their relevance to human smoking, and contrast the acute and chronic effects of nicotine. 

It is well established that acetylcholine can be catabolized by both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) these are also known as "true" and "pseudo" cholinesterase, respectively. Such enzymes may be differentiated by their specificity for different choline esters and by their susceptibility to different antagonists. They also differ in their anatomical distribution, with AChE being associated with nervous tissue while BChE is largely found in non-nervous tissue. In the brain there does not seem to be a good correlation between the distribution of cholinergic terminals and the presence of AChE, choline acetyltransferase having been found to be a better marker of such terminals. An assessment of cholinesterase activity can be made by examining red blood cells, which contain only AChE, and plasma. 

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