Search results for "choline"

Time estimation in minimally abstinent smokers

1998

Metabolic profiling reveals distinct variations linked to nicotine consumption in humans--first results from the KORA study.

2008

Exposure to nicotine during smoking causes a multitude of metabolic changes that are poorly understood. We quantified and analyzed 198 metabolites in 283 serum samples from the human cohort KORA (Cooperative Health Research in the Region of Augsburg). Multivariate analysis of metabolic profiles revealed that the group of smokers could be clearly differentiated from the groups of former smokers and non-smokers. Moreover, 23 lipid metabolites were identified as nicotine-dependent biomarkers. The levels of these biomarkers are all up-regulated in smokers compared to those in former and non-smokers, except for three acyl-alkyl-phosphatidylcholines (e.g. plasmalogens). Consistently significant r…

Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.

2014

Despite the large number of studies available on nicotinic acetylcholine receptors, a complete account of the mechanistic aspects of their gating transition in response to ligand binding still remains elusive. As a first step toward dissecting the transition mechanism by accelerated sampling techniques, we study the ligand-induced conformational changes of the acetylcholine binding protein (AChBP), a widely accepted model for the full receptor extracellular domain. Using unbiased Molecular Dynamics (MD) and Temperature Accelerated Molecular Dynamics (TAMD) simulations we investigate the AChBP transition between the apo and the agonist-bound state. In long standard MD simulations, both confo…

Molecular Histochemistry of Nicotinic Receptors in Human Brain

1997

Only a decade ago the existence and functional significance of central nervous nicotinic acetylcholine receptors (nAChR) was still a subject of controversy. Today, the importance of this receptor class for signal transduction in human brain in normal and pathological conditions has become quite evident. nAChRs have turned out to be important pharmacological targets in disorders like Alzheimer’s disease (AD) (Arneric et al., 1994). One prerequisite to understand nAChR function is a detailed study of the cellular distribution of nAChR subtypes. In recent years several human-specific data have been made available. This paper attempts to show actual developments in this field, summarizing the e…

Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel

1991

AbstractThe reversible acetylcholine esterase inhibitor (−)-physostigmine (eserine) is the prototype of a new class of nicotinic acetylcholine receptor (nAChR) activating ligands: it induces cation fluxes into nAChR-rich membrane vesicles from Torpedo marmorala electric tissue even under conditions of antagonist blocked acetylcholine binding sites (Okonjo, Kuhlmann, Maclicke, Neuron, in press). This suggests that eserine exerts its channel-activating property via binding sites at the nAChR separate from those of the natural transmitter. We now report that eserine can activate the channel even when the receptor has been preincubated (desensitized) with elevated concentrations of acetylcholin…

Activation of Muscarinic Receptors by Non-neuronal Acetylcholine

2011

The biological role of acetylcholine and the cholinergic system is revisited based particularly on scientific research early and late in the last century. On the one hand, acetylcholine represents the classical neurotransmitter, whereas on the other hand, acetylcholine and the pivotal components of the cholinergic system (high-affinity choline uptake, choline acetyltransferase and its end product acetylcholine, muscarinic and nicotinic receptors and esterase) are expressed by more or less all mammalian cells, i.e. by the majority of cells not innervated by neurons at all. Moreover, it has been demonstrated that acetylcholine and “cholinergic receptors” are expressed in non-neuronal organism…

Chapter 8 Nicotinic receptors of the vertebrate CNS: introductory remarks

1996

Publisher Summary This chapter focuses on the nicotinic receptors of the vertebrate central nervous system (CNS). In vertebrates, nicotinic cholinergic neurotransmission is found in both the CNS and the periphery (muscle endplate). Although muscle and neuronal nicotinic acetylcholine receptors (nAChR) have evolved from a common ancestor, it is striking that the muscle receptor has remained rather stable in evolution, whereas the neuronal receptor has evolved to a wide diversity of subtypes. As an attractive hypothesis, neurotransmitters and neurohormones may not only interact with their archetypic cognate receptors but also with other neuroreceptor, albeit in a modulatory fashion. By modula…

Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase express…

2013

The present study investigated the time-course for aging-associated effects on contractile and relaxing vascular responses and nitric oxide (NO) production in the aorta from female senescence-accelerated resistant (SAMR1) and prone (SAMP8) mice. Both SAMR1 and SAMP8 were studied at three different ages: 3 (young), 6 (middle age) and 10 (old) months. Concentration-response curves to phenylephrine (10(-8) to 10(-5) M) or acetylcholine (10(-9) to 10(-5) M) were performed in the aortic rings in the absence or in the presence of NO synthase (NOS) inhibitor L-NAME (10(-4) M). Protein and gene expression for endothelial NOS (eNOS) was determined by immunofluorescence, Western blot and real-time PC…

Effects of ouabain on human bronchial muscle in vitro

2003

The effects of ouabain, an inhibitor of the plasmalemmal Na(+)/K(+)-ATPase activity, were examined in human isolated bronchus. Ouabain produced concentration-dependent contraction with -logEC(50)=7.16+/-0.11 and maximal effect of 67+/-4% of the response to acetylcholine (1 mM). Ouabain (10 microM)-induced contraction was epithelium-independent and was not depressed by inhibitors of cyclooxygenase and lipoxygenase, antagonists of muscarinic, histamine H(1)-receptors and alpha-adrenoceptors, or neuronal Na(+) channel blockade. The inhibition of ouabain contraction in tissues bathed in K(+)-free medium, and the inhibition by ouabain of the K(+)-induced relaxation confirm that the contractile a…

NANC inhibitory neurotransmission in mouse isolated stomach: Involvement of nitric oxide, ATP and vasoactive intestinal polypeptide

2003

1. The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2. Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 3. The inhibitor of the synthesis of nitric oxide (NO), L-NAME, abolished the rapid relaxation and significantly reduced the slow relaxation. Apamin, blocker of Ca 2+-dependent K + channels, or ADPβS, which desensitises P 2y purinoceptors, reduced the slow relaxation to 2-8 Hz, without affecting that to 16-32 Hz or the…