Neurotransmitter Review

Total Page:16

File Type:pdf, Size:1020Kb

Neurotransmitter Review NEUROTRANSMITTER REVIEW the brain with potent opiate agonist activity. Nature 258:577–579, 1975. One chemical that modifies (i.e., modulates) brain func- O’BRIEN, C.P.; VOLPICELLI, L.A.; AND VOLPICELLI, J.R. Naltrexone in the tion and has been implicated in several of alcohol’s acute treatment of alcoholism: A clinical review. Alcohol 13(1):35–39, 1996. and chronic effects is adenosine. This article reviews cur- rent knowledge about alcohol’s interactions with adenosine- PERT, C.B., AND SNYDER, S.H. Opiate receptor: Demonstration in nervous tissue. Science 179:1011–1014, 1973. mediated modulation of nerve-cell activity in the central nervous system (CNS). After summarizing adenosine’s role PERT, A.; PERT, C.B.; DAVIS, G.C.; AND BUNNEY, W.E., JR. Opiate pep- tides and brain function. In: van Praag, E., ed. Handbook of Biological in signal transmission in the CNS, this article discusses Psychiatry. Part 4. New York: Marcel Decker, 1981. pp. 547–582. studies investigating alcohol’s interactions with adenosine in cell-culture (i.e., in vitro) models. Finally, the article reviews the evidence that adenosine may be an important THE ROLE OF THE mediator of alcohol’s effects in both animals and humans. NEUROMODULATOR ADENOSINE IN ALCOHOL’S ACTIONS ADENOSINE ISANEUROMODULATOR Signal transmission among nerve cells, or neurons, is me- Douglas P. Dohrman, Ph.D.; Ivan Diamond, diated primarily by neurotransmitter molecules that are M.D., Ph.D.; and Adrienne S. Gordon, Ph.D. released from the signal-emitting (i.e., presynaptic) cell and interact with specific molecules (i.e., receptors) on the surface of the signal-receiving (i.e., postsynaptic) cell.1 The interaction between the neuromodulator adenosine This interaction results in the excitation or inhibition of the and adenosine receptors on the surface of neurons mod- postsynaptic cell. Adenosine also alters neuronal activity, ifies the neurons’ responses to neurotransmitters. The ac- thereby affecting behavior; however, it does not meet all tivated adenosine receptors alter the levels of small the requirements for a neurotransmitter. For example, signaling molecules (i.e., second messengers) in the cells. adenosine by itself does not excite or inhibit postsynaptic Depending on the receptors and cells involved, these cells. Instead, adenosine regulates or modulates the activity changes can make it easier or more difficult for neuro- of neurons in response to other neurotransmitters; it is transmitters to excite the cell. Adenosine’s activity is reg- therefore called a neuromodulator. ulated by proteins called nucleoside transporters, which Adenosine is generated in all living cells during the breakdown of adenosine triphosphate (ATP), which occurs carry adenosine into and out of the cell. Alcohol inter- during most energy-requiring chemical reactions in the cell. feres with the function of the adenosine system. For ex- Large, channel-forming proteins2 called nucleoside trans- ample, both acute and chronic alcohol exposure affect porters then carry some of the adenosine out of the cells the function of the adenosine-carrying nucleoside trans- into the fluid surrounding the cells (i.e., the extracellular porters, thereby indirectly altering the second-messenger fluid). In addition, some neurons release ATP along with levels in the cells. Through this mechanism, adenosine their neurotransmitters. This ATP also is converted into may mediate some of alcohol’s effects, such as intoxica- adenosine. The adenosine in the extracellular fluid can tion, motor incoordination, and sedation. KEY WORDS: interact with receptors on the surfaces of surrounding cells adenosine; neurotransmitters; receptors; neuron; cell sig- (including the cell that released it) and modulate these cells’ naling; second messenger; nucleosides; biological trans- port; brain; central nervous system; animal cell line; DOUGLAS P. DOHRMAN, PH.D., is a postdoctoral fellow in human cell line; cAMP; signal transduction; AOD intox- the Department of Neurology; IVAN DIAMOND, M.D., PH.D., is professor and vice chairman in the Department of ication; motor coordination; sleep; literature review Neurology, a professor in the Department of Cellular and Molecular Pharmacology, and a member of the lcohol abuse and dependence are among the most Neuroscience Program; and ADRIENNE S. GORDON, PH.D., common and costly health problems worldwide. In is a professor in the Departments of Neurology and Athe United States alone, nearly 7 percent of adults Cellular and Molecular Pharmacology and a member of are alcohol dependent. Furthermore, the consequences of the Neuroscience Program, Ernest Gallo Clinic and heavy drinking account for more than 20 percent of all Research Center, University of California, San Francisco hospitalizations (Diamond and Gordon 1997). To address General Hospital, San Francisco, California. the plethora of medical and social problems associated with alcohol abuse and dependence and to identify the 1Whereas the presynaptic cell is always a neuron, the postsynaptic cell mechanisms underlying the development of tolerance to can be either a neuron or another cell type, such as a muscle cell. and dependence on alcohol, it is vital to understand alco- 2For a definition of this and other technical terms used in this article, see hol’s interactions with various brain systems. central glossary, pp. 177–179. 136 ALCOHOL HEALTH & RESEARCH WORLD NEUROTRANSMITTER REVIEW Adenosine A1 A2 Phospholipase C Adenylyl G Inhibitory cyclase Stimulatory protein G protein G protein produces activates inhibits activates produces Diacylglycerol cAMP activates activates Protein kinase C Protein kinase A Phosphorylation of certain proteins Phosphorylation of certain proteins Figure 1 The adenosine A1 and A2 receptors affect cell function by modulating the activities of the enzymes adenylyl cyclase and phospholipase C. Through their association with inhibitory and stimulatory G proteins, A1 inhibits and A2 activates adenylyl cyclase, the enzyme that produces the second messenger cAMP. In turn, cAMP activates the enzyme protein kinase A (PKA), which adds phosphate groups to (i.e., phosphorylates) various proteins. For example, PKA phosphorylates protein channels, which allow the transport of ions across the cell membrane, and transcription factors, which alter gene activity. Phosphorylation modifies the activities of these proteins. A1 also activates phospholipase C, which produces the second messenger diacylglycerol. This substance activates the enzyme protein kinase C, which also phosphorylates certain proteins. functions. To prevent adenosine accumulation in the extra- an adenosine receptor into changes in cell function requires cellular fluid and control adenosine’s effects on other cells, multiple steps, as follows (see also figure 1): adenosine is taken back up into the cells by the nucleoside transporters or broken down by extracellular enzymes. 1. The adenosine receptors are linked to regulatory molecules called G proteins. Two types of G proteins exist: stimula- Adenosine Receptors tory G proteins (Gs), which enhance the activities of other enzymes, and inhibitory G proteins (G ), which inhibit the Three different subgroups of adenosine receptors exist—A , i 1 activities of other enzymes. The interaction of adenosine A , and A —which differ in their structures and in the 2 3 with its receptors activates Gs or Gi proteins, depending molecules with which they can interact, in addition to adeno- on the receptor involved. sine (for a review, see Palmer and Stiles 1995). Each cell can carry more than one type of adenosine receptor. All 2. Certain activated Gs stimulate and activated Gi inhibit adenosine receptors modulate cell function primarily by the activity of the enzyme adenylyl cyclase, which gen- altering the levels of small signaling molecules (i.e., second erates cAMP. messengers) within the cells. Two important second messen- gers are cyclic adenosine monophosphate (cAMP) and dia- 3. cAMP activates PKA. cylglycerol (DAG). These compounds activate two enzymes (i.e., protein kinase A [PKA] and protein kinase C [PKC]), 4. A different set of G proteins modulates the activity of which add phosphate groups to other proteins. This process the enzyme phospholipase C, which generates DAG. is called phosphorylation. In this way, PKA and PKC acti- vate or inactivate these proteins. Translating the activation of 5. DAG activates PKC. VOL. 21, NO. 2, 1997 137 NEUROTRANSMITTER REVIEW 6. Both PKA and PKC phosphorylate numerous proteins, A1 and A2 receptors. In these cells, adenosine’s overall ef- including receptors for other neurotransmitters; proteins fect on cell functioning likely reflects the ratio of A1 to A2 that form channels allowing charged particles (i.e., ions) receptors. In addition, experimental evidence suggests that to enter or leave the cell; and certain proteins called the same receptor type can have different effects in different transcription factors, which regulate the activity of areas of the same cell and that A1 and A2 receptors can be many genes in the cell nucleus. concentrated in different regions of one cell (LeVier et al. 1992). Both of these mechanisms would create additional 7. As a result of this phosphorylation, the electrical proper- ways for adenosine to modulate neuronal activity. ties of the cell change, making it easier or more difficult to excite the cell, depending on which ion channels are Adenosine Modulates the Functions of Other affected. The phosphorylation of transcription factors Neurotransmitters can
Recommended publications
  • The Creation of Neuroscience
    The Creation of Neuroscience The Society for Neuroscience and the Quest for Disciplinary Unity 1969-1995 Introduction rom the molecular biology of a single neuron to the breathtakingly complex circuitry of the entire human nervous system, our understanding of the brain and how it works has undergone radical F changes over the past century. These advances have brought us tantalizingly closer to genu- inely mechanistic and scientifically rigorous explanations of how the brain’s roughly 100 billion neurons, interacting through trillions of synaptic connections, function both as single units and as larger ensem- bles. The professional field of neuroscience, in keeping pace with these important scientific develop- ments, has dramatically reshaped the organization of biological sciences across the globe over the last 50 years. Much like physics during its dominant era in the 1950s and 1960s, neuroscience has become the leading scientific discipline with regard to funding, numbers of scientists, and numbers of trainees. Furthermore, neuroscience as fact, explanation, and myth has just as dramatically redrawn our cultural landscape and redefined how Western popular culture understands who we are as individuals. In the 1950s, especially in the United States, Freud and his successors stood at the center of all cultural expla- nations for psychological suffering. In the new millennium, we perceive such suffering as erupting no longer from a repressed unconscious but, instead, from a pathophysiology rooted in and caused by brain abnormalities and dysfunctions. Indeed, the normal as well as the pathological have become thoroughly neurobiological in the last several decades. In the process, entirely new vistas have opened up in fields ranging from neuroeconomics and neurophilosophy to consumer products, as exemplified by an entire line of soft drinks advertised as offering “neuro” benefits.
    [Show full text]
  • Apoptosis in the Resolution of Systemic Inflammation
    Apoptosis in the Resolution of Systemic Inflammation J. c. Marshall and R. W. G. Watson Introduction Admission to a contemporary leU is precipitated by a heterogeneous group of dis­ ease processes, yet the final common pathway to death is strikingly similar [I). Fully 80% of all leu deaths occur in association with the multiple organ dysfunction syn­ drome (MODS) [2), a poorly understood process characterized by the development of progressive physiologic dysfunction in organ systems initially unaffected by the primary disease process. Activation of a host inflammatory response by infection, injury, or ischemia, invariably proceeds the development of MODS [3). The proxi­ mate causes of organ injury are not bacterial products, but the same endogenous host-derived mediators of inflammation that are responsible for containing an in­ fectious challenge and initiating the process of tissue repair. MODS can be concep­ tualized as the consequence of an overly activated or inappropriately prolonged systemic inflammatory response, therefore an understanding of the mechanisms underlying the resolution of inflammation is important to the development of clini­ cal strategies to prevent the syndrome. The Resolution of Inflammation Mechanisms As important to the host as the ability to activate an efficient response to an exoge­ nous threat, is the ability to terminate that response once the threat has passed. Both humoral and cellular counter-inflammatory mechanisms have been identified. Monocyte-mediated non-specific responses are regulated through autocrine and paracrine pathways involving the release of counter-inflammatory mediators such as lL-IO [4) or lL-lra [5) that restore the cell to a resting state. For the neutrophil, however, the expression of an inflammatory response results both in the extravasa­ tion of large numbers of cells into an inflammatory focus, and in the activation of these cells for antimicrobial activity.
    [Show full text]
  • Epigenetic Pathways Through Which Experiences Become Linked with Biology
    Development and Psychopathology 27 (2015), 637–648 # Cambridge University Press 2015 doi:10.1017/S0954579415000206 Epigenetic pathways through which experiences become linked with biology a b PATRICK O. MCGowan AND TANIA L. ROTH aUniversity of Toronto; and bUniversity of Delaware Abstract This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this Special Issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g., DNA methylation) that are responsive to environmental input and serve as biological pathways in behavioral development. Here we highlight the experimental evidence, mainly from animal models, that factors such as psychosocial stress and environmental adversity can become encoded within epigenetic factors with functional consequences for brain plasticity and behavior. We also highlight evidence that epigenetic marking of genes in one generation can have consequences for future generations (i.e., inherited), and work with humans linking epigenetics, cognitive dysfunction, and psychiatric disorder. Though epigenetics has offered more of a beginning than an answer to the centuries-old nature–nurture debate, continued research is certain to yield substantial information regarding biological determinants of central nervous system changes and behavior with relevance for the study of developmental psychopathology. Experiences, particularly those occurring during sensitive peri- To better understand the consequences of early and later- ods of development, are well recognized for their ability to ca- life stress on epigenetic mechanisms in this capacity, this nalize neurobiological trajectories and yield significant conse- has required the utilization of experimental rodent models quences for lifelong health and mental well-being.
    [Show full text]
  • Neurobiology and Behavior (NEURBIO) 1
    Neurobiology and Behavior (NEURBIO) 1 Neurobiology and Behavior (NEURBIO) Courses NEURBIO 200A. Research in Neurobiology and Behavior. 2-12 Units. Individual research with Neurobiology and Behavior faculty. Repeatability: Unlimited as topics vary. Restriction: Graduate students only. Neurobiology and Behavior Majors only. NEURBIO 200B. Research in Neurobiology and Behavior. 2-12 Units. Individual research with Neurobiology and Behavior faculty. Prerequisite: NEURBIO 200A Repeatability: Unlimited as topics vary. Restriction: Graduate students only. Neurobiology and Behavior Majors only. NEURBIO 200C. Research in Neurobiology and Behavior. 2-12 Units. Individual research with Neurobiology and Behavior faculty. Prerequisite: NEURBIO 200B Repeatability: Unlimited as topics vary. Restriction: Graduate students only. Neurobiology and Behavior Majors only. NEURBIO 201A. Research in Neurobiology and Behavior. 2-12 Units. Individual research with Neurobiology and Behavior faculty. Grading Option: Satisfactory/unsatisfactory only. Repeatability: Unlimited as topics vary. Restriction: Graduate students only. Neurobiology and Behavior Majors only. NEURBIO 201B. Research in Neurobiology and Behavior. 2-12 Units. Individual research with Neurobiology and Behavior faculty. Prerequisite: NEURBIO 201A Grading Option: Satisfactory/unsatisfactory only. Repeatability: Unlimited as topics vary. Restriction: Graduate students only. Neurobiology and Behavior Majors only. NEURBIO 201C. Research in Neurobiology and Behavior. 2-12 Units. Individual research with Neurobiology and Behavior faculty. Prerequisite: NEURBIO 201B Grading Option: Satisfactory/unsatisfactory only. Repeatability: Unlimited as topics vary. Restriction: Graduate students only. Neurobiology and Behavior Majors only. NEURBIO 202A. Foundations of Neuroscience. 2 Units. Intended to expose students to critical reading and analysis of the primary neuroscience literature. Instructors from departments associated with the Interdepartmental Neuroscience Program participate and discuss topics of current interest.
    [Show full text]
  • Odorant Receptors: Regulation, Signaling, and Expression Michele Lynn Rankin Louisiana State University and Agricultural and Mechanical College, [email protected]
    Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 2002 Odorant receptors: regulation, signaling, and expression Michele Lynn Rankin Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Recommended Citation Rankin, Michele Lynn, "Odorant receptors: regulation, signaling, and expression" (2002). LSU Doctoral Dissertations. 540. https://digitalcommons.lsu.edu/gradschool_dissertations/540 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. ODORANT RECEPTORS: REGULATION, SIGNALING, AND EXPRESSION A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy In The Department of Biological Sciences By Michele L. Rankin B.S., Louisiana State University, 1990 M.S., Louisiana State University, 1997 August 2002 ACKNOWLEDGMENTS I would like to thank several people who participated in my successfully completing the requirements for the Ph.D. degree. I thank Dr. Richard Bruch for giving me the opportunity to work in his laboratory and guiding me along during the degree program. I am very thankful for the support and generosity of my advisory committee consisting of Dr. John Caprio, Dr. Evanna Gleason, and Dr. Jaqueline Stephens. At one time or another, I performed experiments in each of their laboratories and include that work in this dissertation.
    [Show full text]
  • Neuroscience Major Requirements (Fall 2017 Or Later)
    Neuroscience Major Requirements (Fall 2017 or later) Undergraduate Program in Neuroscience : 1140 Undergrad. Science Bldg. (USB) : http://www.lsa.umich.edu/neurosci : [email protected] : 734-763-7984 (front desk) Why study Neuroscience? Neuroscience is the study of the nervous system. Neuroscientists aim to understand how the nervous system develops and functions on a cellular level as well as the mechanisms that underlie behavior, mental disorders and disease. The faculty teaching courses in the major include cellular and molecular neuroscientists appointed in the Department of Molecular, Cellular and Developmental Biology (MCDB) and behavioral and cognitive neuroscientists appointed in the Department of Psychology. This interdisciplinary program gives students the best of both of these worlds. Who should major in Neuroscience? Any student who wishes to pursue a career studying the nervous system or behavior. This is an excellent major for anyone interested in pre-health careers, graduate studies, or careers in the biotech industry. Exclusions: Students who elect a major in Neuroscience may not elect the following majors: Biochemistry Biology Biology, Health & Society (BHS) Biomolecular Science (BMS) Biopsychology, Cognition and Neuroscience (BCN) Cellular & Molecular Biology (CMB) CMBS (formerly CMB:BME) Molecular, Cellular, and Developmental Biology (MCDB) Microbiology Plant Biology Students who elect a major in Neuroscience may not elect a minor in Biology, Plant Biology, Chemistry, or Biochemistry. Students can double major in Psychology and Neuroscience or Cognitive Science and Neuroscience, but may only share a maximum of 3 courses between their two programs. How do I declare? Students interested in neuroscience are encouraged to meet with an advisor to discuss their academic plans as soon as possible! Students need not have completed all of the prerequisites of the major to declare, but should usually have completed the biology introductory sequence with a 2.0 or better and be in good academic standing.
    [Show full text]
  • Lori Knackstedt
    Lori A. Knackstedt, PhD Psychology Department 114 Psychology Building P.O. Box 112250 Gainesville, FL 32611 Email: [email protected] Education Ph.D. 2005: Psychology; University of California, Santa Barbara, Santa Barbara, CA Advisor: Aaron Ettenberg Dissertation: “Motivating Factors Underlying the Co-administration of Cocaine and Alcohol” B.S. 1999: Bucknell University, Lewisburg, PA Major: Biology Magna cum laude Positions Held ______ 2012-present Assistant Professor Psychology Department University of Florida, Gainesville, FL 2008-2012 Research Assistant Professor Neurosciences Department Medical University of South Carolina, Charleston, SC 2005-2008 Post-doctoral Fellow Neurosciences Department Medical University of South Carolina, Charleston, SC Mentor: Peter Kalivas Teaching Experience 2010-2012 Lecturer: MUSC College of Medicine Lectured in the Neuroscience course component for 1rst year medical students and taught the 2 week neuroscience component of Gross Anatomy Lab 2005-2012 Adjunct Faculty: Psychology Dept., College of Charleston, Charleston, SC “PSYCH 103: Introduction to Psychological Science” “PSYCH 388: Psychology of Substance Abuse” “PSYCH 214: Behavioral Neuroscience” 2003-2004 Adjunct Faculty: Psych. Dept., Santa Barbara City College, Santa Barbara, CA “PSY 110: Intro to Physiological Psychology” C.V. Knackstedt 2 2003-2004 Instructor: University of California, Santa Barbara, Santa Barbara, CA “PSYCH 111: Concepts in Biological Psychology” “PSYCH 106: Brain and Behavior” Research Support Ongoing: NIDA: R01 DA033436 (PI:
    [Show full text]
  • Systematic Reconstruction of Autism Biology with Multi-Level Whole
    bioRxiv preprint doi: https://doi.org/10.1101/052878; this version posted May 11, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. 1 Systematic Reconstruction of Autism Biology with Multi-Level 2 Whole Exome Analysis 3 4 Weijun Luo1,2*, Chaolin Zhang3, Cory R. Brouwer1,2 5 1Department of Bioinformatics and Genomics, UNC Charlotte, Charlotte, NC 28223 6 2UNC Charlotte Bioinformatics Service Division, North Carolina Research Campus, 7 Kannapolis, NC 28081 8 3Department of Systems Biology, Department of Biochemistry and Molecular 9 Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New 10 York, New York 10032, USA 11 *Correspondence: [email protected] 12 13 14 Abstract 15 Whole exome/genome studies on autism spectrum disorder (ASD) identified thousands of 16 variants, yet not a coherent and systematic disease mechanism. We conduct novel 17 integrated analyses across multiple levels on ASD exomes. These mutations do not recur 18 or replicate at variant level, but significantly and increasingly so at gene and pathway 19 level. Genetic association reveals a novel gene+pathway dual-hit model, better explaining 20 ASD risk than the well-accepted mutation burden model. 21 In multiple analyses with independent datasets, hundreds of variants or genes consistently 22 converge to several canonical pathways. Unlike the reported gene groups or networks, 23 these pathways define novel, relevant, recurrent and systematic ASD biology. At sub- 24 pathway level, most variants disrupt the pathway-related gene functions, and multiple 25 interacting variants spotlight key modules, e.g.
    [Show full text]
  • Biochem II Signaling Intro and Enz Receptors
    Signal Transduction What is signal transduction? Binding of ligands to a macromolecule (receptor) “The secret life is molecular recognition; the ability of one molecule to “recognize” another through weak bonding interactions.” Linus Pauling Pleasure or Pain – it is the receptor ligand recognition So why do cells need to communicate? -Coordination of movement bacterial movement towards a chemical gradient green algae - colonies swimming through the water - Coordination of metabolism - insulin glucagon effects on metabolism -Coordination of growth - wound healing, skin. blood and gut cells Hormones are chemical signals. 1) Every different hormone binds to a specific receptor and in binding a significant alteration in receptor conformation results in a biochemical response inside the cell 2) This can be thought of as an allosteric modification with two distinct conformations; bound and free. Log Dose Response • Log dose response (Fractional Bound) • Measures potency/efficacy of hormone, agonist or antagonist • If measuring response, potency (efficacy) is shown differently Scatchard Plot Derived like kinetics R + L ó RL Used to measure receptor binding affinity KD (KL – 50% occupancy) in presence or absence of inhibitor/antagonist (B = Receptor bound to ligand) 3) The binding of the hormone leads to a transduction of the hormone signal into a biochemical response. 4) Hormone receptors are proteins and are typically classified as a cell surface receptor or an intracellular receptor. Each have different roles and very different means of regulating biochemical / cellular function. Intracellular Hormone Receptors The steroid/thyroid hormone receptor superfamily (e.g. glucocorticoid, vitamin D, retinoic acid and thyroid hormone receptors) • Protein receptors that reside in the cytoplasm and bind the lipophilic steroid/thyroid hormones.
    [Show full text]
  • Peptide and Amine Actions on the Neurogenic Limulus Heart: Biochemical Mechanisms of Modulation James Richard Groome University of New Hampshire, Durham
    University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Spring 1988 Peptide and amine actions on the neurogenic Limulus heart: Biochemical mechanisms of modulation James Richard Groome University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Groome, James Richard, "Peptide and amine actions on the neurogenic Limulus heart: Biochemical mechanisms of modulation" (1988). Doctoral Dissertations. 1532. https://scholars.unh.edu/dissertation/1532 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. INFORMATION TO USERS The most advanced technology has been used to photo­ graph and reproduce this manuscript from the microfilm master. UMI films the original text directly from the copy submitted. Thus, some dissertation copies are in typewriter face, while others may be from a computer printer. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyrighted material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are re­ produced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each oversize page is available as one exposure on a standard 35 mm slide or as a 17" x 23" black and white photographic print for an additional charge.
    [Show full text]
  • Receptor-Mediated Release of Inositol Phosphates in the Cochlear and Vestibular Sensory Epithelia of the Rat
    207 Hearing Research, 69 (1993) 207-214 0 1993 Elsevier Science Publishers B.V. All rights reserved 037%5955/93/$06.00 HEARES 01970 Receptor-mediated release of inositol phosphates in the cochlear and vestibular sensory epithelia of the rat Kaoru Ogawa and Jochen Schacht Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan, USA (Received 19 January 1993; Revision received 3 May 1993; Accepted 7 May 1993) Various neurotransmitters, hormones and other modulators involved in intercellular communication exert their biological action at receptors coupled to phospholipase C (PLC). This enzyme catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP,) to inositol 1,4,5_trisphosphate (InsP,) and 1,2-diacylglycerol (DG) which act as second messengers. In the organ of Corti of the guinea pig, the InsP, second messenger system is linked to muscarinic cholinergic and Pay purinergic receptors. However, nothing is known about the the InsP, second messenger system in the vestibule. In this study, the receptor-mediated release of inositol phosphates (InsPs) in the vestibular sensory epithelia was compared to that in the cochlear sensory epithelia of Fischer-344 rats. After preincubation of the isolated intact tissues with myo-[“H]in- ositol, stimulation with the cholinergic agonist carbamylcholine or the P, purinergic agonist ATP-y-S resulted in a concentration-dependent increase in the formation of [3H]InsPs in both epithelia. Similarly, the muscarinic cholinergic agonist muscarine enhanced InsPs release in both organs, while the nicotinic cholinergic agonist dimethylphenylpiperadinium (DMPP) was ineffective. The muscarinic cholinergic antagonist atropine completely suppressed the InsPs release induced by carbamylcholine, while the nicotinic cholinergic antagonist mecamylamine was ineffective.
    [Show full text]
  • Chapter 5 Control of Cells by Chemical Messengers = How Hormones and Other Signals Work
    Chapter 5 Control of Cells by Chemical Messengers = How hormones and other signals work Intercellular Communication = Intercellular Signal Transmission •Chemical communication •Electrical communication Intercellular signal transmission • Chemical transmission – Chemical signals • Neurotransmitters: Intercellular signal transmission • Chemical transmission – Chemical signals • Neurotransmitters: • Humoral factors: – Hormones – Cytokines – Bioactivators Intercellular signal transmission • Chemical transmission – Chemical signals • Neurotransmitters: • Humoral factors: • Gas: NO, CO, etc. Communication requires: signals (ligands) and receptors (binding proteins). The chemical properties of a ligand predict its binding site: • Hydrophobic/lipid-soluble: cytosolic or nuclear receptors examples: steroid hormones, thyroid hormones… • Hydrophilic/lipid-insoluble: membrane-spanning receptors examples: epinephrine, insulin… Receptors are proteins that can bind only specific ligands and they are linked to response systems. • Hydrophobic signals typically change gene expression, leading to slow but sustained responses. • Hydrophilic signals typically activate rapid, short-lived responses that can be of drastic impact. Intercellular signal transmission • Chemical transmission – Chemical signals – Receptors • Membrane receptors • Intracellular receptors Intercellular signal transmission • Electrical transmission Gap junction Cardiac Muscle Low Magnification View The intercalated disk is made of several types of intercellular junctions. The gap junction
    [Show full text]