Sympathetic Neurons Expressing Cholinergic Properties Are Poised
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Acetylcholine Signaling System in Progression of Lung Cancers
Pharmacology & Therapeutics 194 (2019) 222–254 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Acetylcholine signaling system in progression of lung cancers Jamie R. Friedman a,1, Stephen D. Richbart a,1,JustinC.Merritta,KathleenC.Browna, Nicholas A. Nolan a, Austin T. Akers a, Jamie K. Lau b, Zachary R. Robateau a, Sarah L. Miles a,PiyaliDasguptaa,⁎ a Department of Biomedical Sciences, Joan C. Edwards School of Medicine, 1700 Third Avenue, Huntington, WV 25755 b Biology Department, Center for the Sciences, Box 6931, Radford University, Radford, Virginia 24142 article info abstract Available online 3 October 2018 The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline Keywords: transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyl- Lung cancer transferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetyl- Acetylcholine cholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic Cholinergic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components Proliferation of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend Invasion Anti-cancer drugs is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic ciga- rettes considered by many as a “safe” alternative to smoking. -
Imaging Functional Brain Connectivity
Imaging Functional Brain Connectivity: pharmacological modulation, aging & Alzheimer’s disease Bernadet L. Klaassens 1 Table of contents Chapter 1 3 Introduction and aims Part I: Pharmacological challenge effects on brain connectivity in healthy young adults Chapter 2 10 Single-dose serotonergic stimulation shows widespread effects on functional brain connectivity (NeuroImage 2015 Nov; 122: 440-450) Chapter 3 31 Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation (Human Brain Mapping 2017 Jan; 38 (1): 308-325) Part II: Functional brain connectivity and neuromodulation in older age and Alzheimer’s disease Chapter 4 60 Diminished posterior precuneus connectivity with the default mode network differentiates normal aging from Alzheimer’s disease (Frontiers in Aging Neuroscience 2017 Apr; 9: 1-13) Chapter 5 84 Serotonergic and cholinergic modulation of functional brain connectivity: a comparison between young and older adults ( NeuroImage 2018 Apr; 169: 312-322) Chapter 6 108 Imaging cholinergic and serotonergic neurotransmitter networks in Alzheimer’s disease in vivo (Submission at Alzheimer’s and Dementia) Chapter 7 131 Summary and general discussion 2 Chapter 1 Introduction and aims Brain function relies heavily on neural communication and connections. Better understanding of the mechanisms that are related to maintenance or deterioration of brain function requires a technique that takes into account the elaborate nature of the central nervous system (CNS). A useful method for that purpose is to assess the brain’s functional connectivity. Brain regions are functionally connected to each other when they exhibit correlating activation patterns (Friston et al., 1993), illustrating the complex organization of neural networks. Interactions between regions and within networks largely depend on chemical transmission between neurons. -
The Effect of Oxime Reactivators on the Muscarinic Receptors
Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors Ondrej Soukup1,6, Jan Krusek4, Martina Kaniakova4, Uday Killi. Kumar3, Murat Oz5, Daniel Jun1,2, Josef Fusek1 and Kamil Kuca1,2 and Gunnar Tobin3 1Department of Toxicology and 2Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic 3Institute of Neuroscience and Physiology, Department of Pharmacology, the Sahlgrenska Academy at University of Gothenburg, Sweden 4Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic 5Department of Pharmacology and Therapeutics, Faculty of Medicine, United Arab Emirates University, Al Ain, United Arab Emirates 6University Hospital Hradec Kralove, Czech Republic Corresponding author: Ondrej Soukup ****************************************** Department of Toxicology Faculty of Military Health Sciences University of Defence Trebesska 1575 50001; Hradec Kralove Czech Republic Tel.: +420 973 255 151 Fax: +420 495 518 094 E-mail: [email protected] Summary: Current treatment of organophosphorus poisoning, resulting in overstimulation and desensitization of muscarinic and nicotinic receptors by acetylcholine (ACh), consists of the administration of atropine and oxime reactivators. However, no versatile oxime reactivator has been developed yet and some mortality still remains after application of standard atropine treatment, probably due to its lack of antinicotinic action. In our study, we focused on the interesting non-acetylcholinesterase property of oximes, i.e. antinicotinic effect of reactivators. Two standard reactivators (HI-6, obidoxime) and two new compounds (K027 and K203) were chosen and in vitro (patch clamp) and in vivo (nerve-evoked muscle contraction) testings were applied. Both examinations showed antinicotinic effects of the reactivators. -
(19) 11 Patent Number: 5668117
US005668117A United States Patent (19) 11 Patent Number: 5,668,117 Shapiro 45 Date of Patent: Sep. 16, 1997 54 METHODS OF TREATING NEUROLOGICAL 4,673,669 6/1987 Yoshikumi et al. ...................... 514.f42 DSEASES AND ETOLOGICALLY RELATED 4,757,054 7/1988 Yoshikumi et al. ... 514742 SYMPTOMOLOGY USING CARBONYL 4,771,075 9/1988 Cavazza ............... ... 514/556 TRAPPNGAGENTS IN COMBINATION 4,801,581 1/1989 Yoshikumi et al. ...................... 514.f42 WITH PREVIOUSLY KNOWN 4,874,750 10/1989 Yoshikumi et al. ...................... 514/42 MEDICAMENTS 4,956,391 9/1990 Sapse .................. 514,810 4,957,906 9/1990 Yoshikumi et al. ...................... 514/25 tor: H . Shani 4,983,586 1/1991 Bodor....................................... 514/58 76 Inventor ES pr.) Price Ave 5,015,570 5/1991 Scangos et al. ............................ 435/6 5,037,851 8/1991 Cavazza ........... ... 514,912 5,252,489 10/1993 Macri ........................................ 436/87 21 Appl. No.: 62,201 5297,562 3/1994 Potter. ... 128/898 al 5,324,667 6/1994 Macri. ... 436/87 22 Filed: Jun. 29, 1993 5,324,668 6/1994 Macri ....................................... 436/87 Related U.S. Application Data I63 Continuation-in-part of set No. 26.617, Feb. 23, 1993, Primary Eminer ohn Kight abandoned, which is a continuation of Ser. No. 660.561, Assistant Examiner-Louise Leary Feb. 22, 1991, abandoned. Attorney, Agent, or Firm-D. J. Perrella (51) Int. Cl. ................... A01N 43/04; A01N 61/00; 57 ABSTRACT C07H1/00; C08B 37/08 52 U.S. C. ................................ 514/55; 514/54; 514/23; Therapeutic compositions comprising an effective amount 514/1: 514/811; 514/866; 514/878; 514/879; of at least one carbonyl trapping agent alone or in combi 514/903; 514/912; 436/518; 436/74; 536/1.11; nation with a therapeutically effective of a co-agent or 536/20 medicament are disclosed. -
Vasoactive Intestinal Polypeptide in Cholinergic Neurons of Exocrine
Proc. NatI. Acad. Sci. USA Vol. 77, No. 3, pp. 1651-1655, March 1980 Neurobiology Vasoactive intestinal polypeptide in cholinergic neurons of exocrine glands: Functional significance of coexisting transmitters for vasodilation and secretion (acetylcholinesterase/atropine-resistant vasodilation) JAN M. LUNDBERG*, ANDERS ANGGARDt, JAN FAHRENKRUG§, TOMAS HOKFELT*, AND VIKTOR MUTTf Departments of *Histology, tPharmacology, and tBiochemistry, Karolinska Institutet, Stockholm, Sweden; and §Departments of Clinical Chemistry, Glostrup and Bispebjerg Hospitals, Copenhagen, Denmark Communicated by Rolf Luft, October 18, 1979 ABSTRACT By a combination of the indirect immunoflu- in acetylcholinesterase (acetylcholine acetylhydrolase, EC orescence technique with acetylcholinesterase (acetylcholine 3.1.1.7) (AcChoE)-rich neurons innervating several exocrine acetylhydrolase, EC 3.1.1.7) staining, it was shown that vaso- active intestinal polypeptide (VIP) is present in cholinergic glands. Furthermore, pharmacological effects of VIP and (acetylcholinesterase-rich) neurons involved in control of se- AcCho as well as of various blocking agents, including VIP cretion and vasodilation in exocrine glands of cat. The sub- antiserum, on submandibular salivary secretion and vasodilation mandibular salivary gland was used as a functional model. have been studied. Release of immunoreactive VIP into the Preganglionic nerve stimulation induced an atropine-resistant, venous outflow from the submandibular gland after nerve hexamethonium-sensitive vasodilation and release of VIP into stimulation was the venous outflow from the gland and an atropine- and hexa- also demonstrated. methonium-sensitive secretion. Infusion of VIP antiserum re- duced both the vasodilation and secretion. Infusion of VIP MATERIALS AND METHODS caused vasodilation only, whereas acetylcholine caused both Ten cats (body weight 2-4 kg) of both sexes were used for im- vasodilation and secretion. -
Potencies and Selectivities of Inhibitors of Acetylcholinesterase and Its Molecular Forms in Normal and Alzheimer’S Disease Brain*
Acta Biologica Hungarica 54 (2), pp. 183–189 (2003) POTENCIES AND SELECTIVITIES OF INHIBITORS OF ACETYLCHOLINESTERASE AND ITS MOLECULAR FORMS IN NORMAL AND ALZHEIMER’S DISEASE BRAIN* Z. RAKONCZAY** Alzheimer’s Disease Research Center, Department of Psychiatry, University of Szeged, Szeged, Hungary (Received: April 2, 2003; accepted: April 24, 2003) Eight inhibitors of acetylcholinesterase (AChE), tacrine, bis-tacrine, donepezil, rivastigmine, galanta- mine, heptyl-physostigmine, TAK-147 and metrifonate, were compared with regard to their effects on AChE and butyrylcholinesterase (BuChE) in normal human brain cortex. Additionally, the IC50 values of different molecular forms of AChE (monomeric, G1, and tetrameric, G4) were determined in the cerebral cortex in both normal and Alzheimer’s human brains. The most selective AChE inhibitors, in decreasing sequence, were in order: TAK-147, donepezil and galantamine. For BuChE, the most specific was rivastigmine. However, none of these inhibitors was absolutely specific for AChE or BuChE. Among these inhibitors, tacrine, bis-tacrine, TAK-147, metrifonate and galantamine inhibited both the G1 and G4 AChE forms equally well. Interestingly, the AChE molecular forms in Alzheimer samples were more sensitive to some of the inhibitors as compared with the normal samples. Only one inhibitor, rivastig- mine, displayed preferential inhibition for the G1 form of AChE. We conclude that a molecular form-spe- cific inhibitor may have therapeutic applications in inhibiting the G1 form, which is relatively unchanged -
Carbaryl Human Health and Ecological Risk Assessment Revised Final Report
SERA TR-052-01-05a Carbaryl Human Health and Ecological Risk Assessment Revised Final Report Submitted to: Paul Mistretta, COR USDA/Forest Service, Southern Region 1720 Peachtree RD, NW Atlanta, Georgia 30309 USDA Forest Service Contract: AG-3187-C-06-0010 USDA Forest Order Number: AG-43ZP-D-06-0009 SERA Internal Task No. 52-01 Submitted by: Patrick R. Durkin and Cynthia King Syracuse Environmental Research Associates, Inc. 5100 Highbridge St., 42C Fayetteville, New York 13066-0950 Fax: (315) 637-0445 E-Mail: [email protected] Home Page: www.sera-inc.com February 9, 2008 Table of Contents Table of Contents............................................................................................................................ ii List of Figures................................................................................................................................. v List of Tables .................................................................................................................................. v List of Attachments........................................................................................................................ vi List of Appendices ......................................................................................................................... vi COMMON UNIT CONVERSIONS AND ABBREVIATIONS................................................... ix CONVERSION OF SCIENTIFIC NOTATION ............................................................................ x EXECUTIVE SUMMARY .......................................................................................................... -
The Potential of Cholinesterases As Tools for Biomonitoring Studies with Sharks: Biochemical Characterization in Brain and Muscle Tissues of Prionace Glauca
Journal of Experimental Marine Biology and Ecology 465 (2015) 49–55 Contents lists available at ScienceDirect Journal of Experimental Marine Biology and Ecology journal homepage: www.elsevier.com/locate/jembe The potential of cholinesterases as tools for biomonitoring studies with sharks: Biochemical characterization in brain and muscle tissues of Prionace glauca Luís M. Alves a,b, Marco F.L. Lemos a,b,JoãoP.S.Correiaa,b,c,NunoA.R.daCostaa,SaraC.Novaisa,b,⁎ a ESTM, GIRM, Polytechnic Institute of Leiria, 2520-641 Peniche, Portugal b MARE, Polytechnic Institute of Leiria, Portugal c Flying Sharks, 9900-361 Horta, Portugal article info abstract Article history: Cholinesterases (ChE) are a family of enzymes that play an essential role in neuronal and motor functions. Received 24 September 2014 Because of the susceptibility of these enzymes to anticholinergic agents and to other contaminants, their activity Received in revised form 12 January 2015 is frequently used as biomarker in pollution monitoring studies. The three known types of ChE in fish are Accepted 13 January 2015 acetilcholinesterase (AChE), butyrylcholinesterase (BChE) and propionylcholinesterase (PChE). The presence Available online 29 January 2015 of these enzymes in each tissue differs between species, and thus their usage as biomarkers requires previous en- zyme characterization. Sharks, mostly acting as apex predators, help maintain the balance of fish populations Keywords: Biomarker performing a key role in the ecosystem. Blue sharks (Prionace glauca) are one of the most abundant and heavily Blue shark fished sharks in the world, thus being good candidate organisms for ecotoxicology and biomonitoring studies. Pollution The present study aimed to characterize the ChE present in the brain and muscle of the blue shark using different Chlorpyrifos-oxon substrates and selective inhibitors, and to assess the in vitro sensitivity of these sharks' ChE to chlorpyrifos-oxon, a metabolite of a commonly used organophosphorous pesticide, recognized as a model anticholinesterase contam- inant. -
Neuropeptides and the Innervation of the Avian Lacrimal Gland
Investigative Ophthalmology & Visual Science, Vol. 30, No. 7, July 1989 Copyright © Association for Research in Vision and Ophthalmology Neuropeptides and the Innervation of the Avian Lacrimal Gland Denjomin Wolcorr,* Patrick A. 5ibony,j- and Kent T. Keyser^: The chicken Harderian gland, the major lacrimal gland, has two major cell populations: a cortical secretory epithelium and a medullary interstitial cell population of lymphoid cells. There is an exten- sive acetylcholinesterase (AChE) network throughout the gland, as well as catecholamine positive fibers among the interstitial cells. There are substance P-like (SPLI) and vasoactive intestinal poly- peptide-like (VIPLI) immunoreactivite fibers throughout the gland. These fibers are particularly dense and varicose among the interstitial cells. The adjacent pterygopalatine ganglion complex has neuronal somata that exhibit VIPLI and were AChE-positive. This ganglion complex also contains SPLI and catecholamine-positive fibers. In regions of the ganglion, the somata appear surrounded by SPLI varicosities. Surgical ablation of the ganglion eliminated or reduced the VIPLI, AChE and catecholamine staining in the gland. The SPLI was reduced only in some regions. Ablation of the superior cervical ganglion or severance of the radix autonomica resulted in the loss of catecholamine staining in the pterygopalatine ganglion and the gland. Severance of the ophthalmic or infraorbital nerves had no effect on the VIPLI or the SPLI staining pattern in the gland. Invest Ophthalmol Vis Sci 30:1666-1674, 1989 The avian Harderian gland is the major source of further investigation. Using immunohistochemical serous fluid1 and immunoglobulins2 in tears. Like the techniques and surgical ablations, the source, pat- mammalian lacrimal gland, it is innervated by both terns and regional distribution of cholinergic, adren- sympathetic and parasympathetic nerve fibers.34 The ergic and neuropeptide innervation of the chicken avian gland differs from the mammalian lacrimal Harderian gland were studied. -
Cholinomimetic Drugs
Cholinomemtic drugs Pharma 428 Cholinomimetic drugs: The neuron is a communication network that allows an organism to interact with the environment in appropriate ways. The nervous system can be classified to the CNS&PNS. The CNS is composed of the brain and spinal cord. The PNS has both somatic nervous system and autonomic nervous system. What are the differences between the somatic and autonomic nervous system? Somatic Autonomic Controls skeletal muscles. Control smooth muscle of viscera, blood vessels, exocrine glands and cardiac muscle. Voluntary Involuntary One fiber 2 neurons Autonomic nervous system: consist of: 1. Sympathetic or thoracolumbar outflow. Function: fight or flight 2. Parasympathetic or craniosacral outflow. Function: feed or breed 3. Enteric nervous system (mixed preganglionic PARASYMPATHETIC + postganglionic SYMPATHETIC) Innervations by autonomic nervous system: Most of the organs are clearly innervated by both sympathetic and parasympathetic systems but usually one predominates. Some organs as adrenal medulla, kidney, blood vessels, sweat glands and pilomotor muscle (hair muscle) receive only from (sympathetic system). Neurotransmitters: Chemical substances responsible for communication between nerve s with other nerves or with effector organs Neurotransmitter is noradrenaline in adrenergic nerves. (e.g.sympathetic postsynaptic) Neurotransmitter is acetylcholine in cholinergic nerves. (e.g. presynaptic, postganglionic parasympathetic) 1 Cholinomemtic drugs Pharma 428 Cholinergic nervous system:. Chloinergic transmission: Definition :transmission and delivery of the impulses between cholinergic nerves . either between : preganglionic and postganglionic neurons , or between : post ganglionic neuron and the effector organ . Mechanism : 1- The action potential reaches the nerve terminal, carrying depolarization with it. 2- Depolarization causes opening of calcium channels, and so calcium enters the nerve terminal 3- Entry of calcium ions causes release of neurotransmitters like Ach. -
Neuroscience Products
Neuroscience Products CATALOG CATALOG NUMBER U.S. $ NUMBER U.S. $ -A- 3-(N-ACETYLAMINO)-5-(N-DECYL-N- 1 mg 27.50 159549 METHYLAMINO)BENZYL ALCOHOL 5 mg 89.40 o A23187 0-5 C [103955-90-4] (ADMB) See: Antibiotic A23187 A Protein Kinase C activator. Ref.: Proc. Nat. Acad. Sci. USA, 83, 4214 AA-861 20 mg 72.70 (1986). 159061 Purity: 95% 100 mg 326.40 C20H34N2O2 MW 334.5 0oC Orally active, specific and potent inhibitor of 5-lipoxygenase. N-ACETYL-ASP-GLU 25 mg 45.00 153036 [3106-85-2] 100 mg 156.00 Ref.: 1. Yoshimoto, T., et.al., Biochim. o Biophys. Acta, 713, 470 (1982). 2. Ashida, -20-0 C An endogenous neuropeptide with high 250 mg 303.65 Y., et.al., Prostaglandins, 26, 955 (1983). 3. affinity for a brain "Glutamate" receptor. Ancill, R.J., et.al., J. Int. Med. Res., 18, 75 Ref: Zaczek, R., et al., Proc. Natl. Acad. (1990). Sci. (USA), 80, 1116 (1983). C21H26O3 MW 326.4 C11H16N2O8 MW 304.3 ABL PROTEIN TYROSINE KINASE 250 U 47.25 N-ACETYL-2-BENZYLTRYPTAMINE 195876 (v-abl) 1 KU 162.75 See: Luzindole -70oC Recombinant Expressed in E. coli ACETYL-DL-CARNITINE 250 mg 60.00 A truncated form of the v-abl protein 154690 [2504-11-2] 1 g 214.00 tyrosine kinase which contains the 0oC Hydrochloride minimum region needed for kinase activity Crystalline and fibroblast transformation. Suppresses C9H17NO4 • HCl MW 239.7 apoptosis and induces resistance to anti-cancer compounds. O-ACETYL-L-CARNITINE CHLORIDE 500 mg 11.45 Activity: 100 KU/ml 159062 [5080-50-2] 1 g 20.65 Unit Definition: one unit is the amount of 0-5oC (R-(-)-2-Acetyloxy-3-carboxy-N,N,N-trimethyl 5 g 97.45 enzyme which catalyzes the transfer of 1 -1-propanaminium chloride) pmol of phosphate to EAIYAAPFAKKK per Purity: >88% minute at 30°C, pH 7.5. -
Cholinergic Regulation of Neurite Outgrowth from Isolated Chick Sympathetic Neurons in Culture
The Journal of Neuroscience, January 1995, 15(i): 144-151 Cholinergic Regulation of Neurite Outgrowth from Isolated Chick Sympathetic Neurons in Culture David H. Small,’ Gullveig Reed,’ Bryony Whitefield,’ and Victor Nurcombe* Departments of ‘Pathology and 2Anatomy and Cell Biology, The University of Melbourne, and the Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia Neurotransmitters have been reported to regulate neurite mate, serotonin, and dopamine have all beenshown to influence outgrowth in several vertebrate and nonvertebrate species. neurite outgrowth in culture (Mattson, 1988; Lipton and Kater, In this study, cultures of isolated embryonic day 12 (E12) 1989). There is also evidence that ACh could have nonclassical chick sympathetic neurons were grown in the presence of actions in the nervous system (Lankford et al., 1988; Lipton et cholinergic receptor agonists or antagonists. Both ACh and al., 1988; Mattson, 1988). The biosynthetic and degradative the nonhydrolyzable cholinergic agonist carbamylcholine enzymesofcholinergic pathways ChAT and AChE are expressed (CCh) inhibited neurite outgrowth. ACh (0.1-l .O mM) de- in the developing brain well before the major period of syn- creased the percentage of neurons bearing neurites, but had aptogenesis(Filogamo and Marchisio, 1971; Silver, 1974), sug- no significant effect on cell survival. The effect of ACh was gesting that they may be involved in functions unrelated to increased in the presence of the cholinesterase inhibitors neurotransmission. ACh has been shown to suppressneurite BW284C51 (1 MM), Tacrine (20 PM), and edrophonium (200 outgrowth from chick (Lankford et al., 1988) and rat (Lipton et PM). Neurite outgrowth was strongly inhibited by the mus- al., 1988) retinal cells, from hippocampal pyramidal neurons carinic receptor agonist oxotremorine (5-100 PM) and weakly (Mattson, 1988) and to prevent the inhibition of processout- inhibited by nicotine (50 nM to 10 PM).