[PDF] Full Heterogeneity Of Neuronal Nicotinic Acetylcholine Receptors In Rat Nervous System And Their Differential Regulation By Chronic Administration Of Nicotine Download eBook

Heterogeneity of Neuronal Nicotinic Acetylcholine Receptors in Rat Nervous System and Their Differential Regulation by Chronic Administration of Nicotine

Author: Danyan Mao

Publisher:

Published: 2007

Total Pages: 151

ISBN-13: 9780549002963

Neuronal nicotinic acetylcholine receptors (nAChRs) are present throughout the central and peripheral nervous systems. Native nAChRs are not only heterogeneous in subtypes but also complex in subunit composition. In the present study, we used receptor binding and immunoprecipitation methods to examine the nAChRs in a number of peripheral ganglia and brain regions from adult rat. In the periphery, nAChRs were found in superior cervical ganglia (SCG), nodose, stellate, and pelvic ganglia. However, density of the nAChRs in SCG was ∼10 to 50 times higher than those in the other ganglia. A majority of the nAChRs in SCG and nodose ganglia contained alpha3 and beta4 subunits, but a significant fraction of the nAChRs in these ganglia also contained alpha5 and beta2 subunits. Sequential immunoprecipitations in SCG revealed that all alpha5 subunits were associated with alpha3 and beta4 subunits, forming the mixed heteromeric alpha3beta4alpha5 subtype, representing 25--30% of the total heteromeric nAChRs in SCG; also, 55--60% and 10--15% of the nAChRs were simple alpha3beta4 and mixed alpha3beta4beta2 subtype, respectively. In brain, in addition to the predominant alpha4 and beta2 subunits, we found significant fractions of nAChRs contain alpha5 subunit, ranging from ∼one-tenth of the total nAChRs in superior colliculus to more than one-third in hippocampus. Moreover, alpha5 subunit was exclusively incorporated in the alpha4beta2 nAChRs, forming the mixed heteromeric alpha4beta2alpha5 subtype in hippocampus, striatum, cerebral cortex and thalamus. Most importantly, during chronic administration of nicotine in rats, density of the alpha4beta2alpha5 subtype did not change, despite significant up-regulation of the alpha4beta2* and alpha3beta2* nAChRs in brain. This differential regulatory effect of nicotine also extended to other nAChR subtypes. Similar to the alpha4beta2alpha5 subtype, nAChRs containing beta3 subunit in striatum and superior colliculus, most likely in the composition of alpha6beta2beta3*, appeared resistant to regulation by nicotine, whereas the overall density of the alpha6-containing nAChRs decreased in striatum, but remained the same in superior colliculus. The differential regulation by chronic nicotine may not only provide new clues to the mechanisms of nicotine-induced up-regulation of nAChRs in brain, but also have important implications in various aspects of nicotine addiction.

Neuronal Nicotinic Receptors

Author: Francesco Clementi

Publisher: Springer Science & Business Media

Published: 2000

Total Pages: 860

ISBN-13: 9783540661238

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Neuronal nicotinic receptors are key molecules for signal transduction in a number of neuronal pathways. They are widely distributed in the brain and are known to be involved in cognitive tasks, including learning and memory, in smoking addiction and in several brain diseases, such as Alzheimer's and Parkinson's dementias, schizophrenia, and epilepsy. This book provides a comprehensive review of the field, starting with a historical perspective and dealing with the molecular structure of these receptors, their biophysical and pharmacological properties, their distribution in central and peripheral nervous systems, and their major involvement in brain functions. Particular emphasis is paid to drugs (both new and old) that are useful in the diagnosis and treatment of diseases involving neuronal nicotinic receptors. Finally, the relevance of these receptors in smoking addiction is carefully evaluated, together with future trends and the latest results.

Nicotinic Receptors in the Nervous System

Author: Edward D. Levin

Publisher: CRC Press

Published: 2001-08-29

Total Pages: 310

ISBN-13: 1420038524

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Featuring a unique approach, Nicotinic Receptors in the Nervous System provides integrated coverage of research on neuronal nicotinic systems relevant to smoking addiction and cognitive dysfunction. By bringing together molecular and neurochemical applications, the book provides the key to understanding function and dysfunction of nicotinic systems and how they are significant for disease, addiction, and the development of novel drug treatments. The book presents readers with the basic mechanistic background for these treatments as well as the functional assessment necessary to determine therapeutic effects.

Nicotinic Acetylcholine Receptors in the Nervous System

Author: Francesco Clementi

Publisher: Springer Science & Business Media

Published: 2013-06-29

Total Pages: 432

ISBN-13: 3642741673

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The acetylcholine nicotinic receptor is an ionic channel whose aperture is directly controlled by acetylcholine. It is a key molecule in the chemical communication between nerve cells and between nerve cell and muscle. The structure and function of muscular nicotinic receptors have been unraveled in recent years and its beauty and mysteries were reviewed in the Santorini NATO ARW organized by Dr. Maelicke in 1986. The neat, linear structure of this molecule and its conservation throughout evolution, from bacteria to humans, have led to the suggestion that it has reached the optimal structure for performing its function. But when scientists began to look at the nicotinic receptor in the nervous system, they found several surprises. From the beginning, pharmacological and physiological experiments, have made it clear that the functional characteristics of neuronal nicotinic receptors are substantially different from those of muscle receptors. Furthermore, recent sophisticated techniques such as patch clamp and gene cloning have revealed that the nicotinic receptor in the nervous system is not a single molecule but (although there are some important exceptions) a large family of similar molecules, which have in common the property of binding nicotinic agonists or antagonists. Over the last few years, the physiological implications of nicotinic receptors have been reevaluated on the basis of more precise behavioural and pharmacological techniques. Moreover, the involvement of nicotinic receptors in degenerative pathologies of the eNS, such as Parkinson's and Alzheimer's disease, has also been discovered very recently.

Nicotinic Acetylcholine Receptors in Health and Disease

Author: R. Thomas Boyd

Publisher: Academic Press

Published: 2023-03-14

Total Pages: 292

ISBN-13: 0128204184

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Nicotinic Acetylcholine Receptors in Health and Disease provides the latest information Nicotinic acetylcholine receptors (nAChRs), which are involved in numerous diseases, including Alzheimer’s, Parkinson’s, and schizophrenia, and are important potential translational targets for treatment of these diseases, as well as therapy for addiction. This book focuses on the roles and function of nAChRs inside and outside of the nervous system, with an emphasis on translational implications and future prospects for the treatment of numerous disorders. This greater understanding of the basic neurobiology and clinical roles of nAChRs provides important insights for future clinical treatments of many major disorders. Describes the roles, expression and function of nicotinic receptors Includes receptor involvement, both inside and outside the nervous system Details nicotinic receptor involvement in Alzheimer’s, Parkinson’s, Cancer, Schizophrenia, and more Emphasizes future treatment prospects of disorders via modulation of nAChR signaling

How Tobacco Smoke Causes Disease

Author: United States. Public Health Service. Office of the Surgeon General

Publisher:

Published: 2010

Total Pages: 728

ISBN-13:

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This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Presynaptic Receptors and Neuronal Transporters

Author: S.Z. Langer

Publisher: Elsevier

Published: 2013-10-22

Total Pages: 373

ISBN-13: 1483278220

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Advances in the Biosciences, Volume 82: Presynaptic Receptors and Neuronal Transporters documents the proceedings of the Official Satellite Symposium to the IUPHAR 1990 Congress held in Rouen, France on June 26-29, 1990. The first part of this book deals with the extensive and still increasing list of presynaptic release-modulating auto and heteroreceptors, emphasizing the various subtypes of presynaptic receptors that are characterized by functional studies, both in vitro and in vivo, using a number of experimental approaches. The next chapters are devoted to the molecular pharmacology of presynaptic receptors, of which can interfere with G proteins and modify the activity of adenylate cyclase, guanylate cyclase, or protein kinase C. The purification and molecular biology of transporter systems, including cloning and sequencing of the neuronal sodium-ion coupled GABA transporter are also discussed. This compilation concludes with insights on the function of presynaptic receptors and neuronal transporters both in the periphery and in the CNS, as well as their ubiquitous locations and physiological roles. This publication is a good reference for students and individuals researching on the presynaptic autoreceptors and neurotransmitters.