CHOLINERGIC MECHANISMS Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance

ADVANCES IN BEHAVIORAL BIOLOGY

Editorial Board:

Jan Bures Irwin Kopin Bruce McEwen James McGaugh

Institute of Physiology, Prague, Czechoslovakia National Institute of Mental Health, Bethesda, Maryland Rockefeller University, New York, New York University of California, Irvine, California

Karl Pribram Jay Rosenblatt Lawrence Weiskrantz

Stanford University School of Medicine, Stanford, California Rutgers University, Newark, New Jersey University of Oxford, Oxford, England

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CHOLINERGIC MECHANISMS Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance

Edited by

Giancarlo Pepeu Institute of Pharmacology University of Florence Florence, Italy

and

Herbert Ladinsky Mario Negri Institute for Pharmacological Research Milan, Italy

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

Main entry under title:

Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synap­ses, and Clinical Significance.

Proceedings of the International Symposium on Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance, held Mar. 11-15, 1980, in Florence, Italy.

Includes bibliographies and indexes. 1. Acetylcholine - Metabolism - Congresses. 2. Cholinergic receptors - Con­

gresses. 3. Synapses-Congresses. 4. Parasympathomimetic agents- Testing­Congresses. I. Pepeu, Ginacarlo. 11. Ladinsky, Herbert. 111. International Sympo­sium on Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance (1980 : Florence, Italy) IDNLM: 1. Acetyl­choline-Congresses. QV 122 161c 19801 QP921.A25C48 612.8042 81-11936

Proceedings of an International Symposium on Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance, held March 11-15, 1980, in Florence, Italy

© 1981 Plenum Press, New York Softcover reprint of the hardcover 1 st edition 1981

A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013

All rights reserved

AACR2

No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission trom the publisher

ISBN 978-1-4684-8645-2 ISBN 978-1-4684-8643-8 (eBook)DOI 10.1007/978-1-4684-8643-8

SPONSORED BY

Societa Italiana di Farmacologia

International Union Pharmacology (IUPHAR)

Consiglio Nazionale delle Ricerche

ACKNOWLEDGMENT

The Symposium has been made possible by a

grant from the Consiglio Nazionale delle

Ricerche and by the generous support of

Fidia Research Laboratoreis, Abano Terme

(Padua) Italy.

ORGANIZING COMMITTEE

Lorenzo Beani Department of Pharmacology University of Ferrara Ferrara, Italy

Edith Heilbronn Unit of Neurochemistry and

Neurotoxicology University of Stockholm Stockholm, Sweden

Donald J. Jenden Department of Pharmacology School of Medicine University of California Los Angeles, California

Alexander Karczmar Department of Pharmacology Stritch School of Medicine Loyola University Maywood, Illinois

vi

Herbert Ladinsky The Mario Negri Institute for Pharmacological Research Milan, Italy

Peter G. Waser Institute of Pharmacology University of Zurich Zurich, Switzerland

Victor P. Whittaker Max-Planck Institut for Biomedical Research Gottingen, FR Germany

Giancar10 Pepeu, Chairman Department of Pharmacology University of Florence Florence, Italy

PREFACE

Every three years early Spring witnesses the convening of a small group of neuroscientists from many parts of the world. They are devoted to the study of acetylcholine, the oldest of the known neurotransmitters. To assess the level of knowledge, to take stock of the still unsolved problems, to evaluate the practical meaning of their findings, the cholinologists first met in 1969 in the eerie atmosphere of a snow-covered Swedish forest, the second in the Swiss Alps, the third facing the surf and foam of the Paci­fic waves. Finally in March 1980 Florence, her trees burgeoning in the mild rain of March, confronted them with the temptation of her monuments and museums. But the cholinologists bravely dismis­sed the temptations and went on with the presentations and discus­sions of the many papers which form the present book.

The papers describe the most recent development of investiga­tions on acetylcholine. They open with an extensive coverage of the developmental and phylogenetic aspects of the cholinergic neurons. The regulation of acetylcholine synthesis, release, post­synaptic, electrical and trophic effects in the peripheral chol­inergic synapses including ganglia, neuromuscular junction, myen­theric plexus and heart is then covered. Special emphasis is given to the cholinergic mechanisms in the eye. But the largest part of the papers are devoted to the central cholinergic synapse, to the possibility of influencing its function through drugs and precursors and to the clinical meaning of the most recent findings in this realm. The fast moving knowledge on the central cholinergic recep­tors, the elusive central cholinergic pathways, the complex inter­actions between acetylcholine and other neurotransmitter systems also are the topic of several pages.

Many young scientists have joined in recent years the cholin­ergic field and to them was given the opportunity to present their work together with that of many old hands in this business. The book is a blend of basic and clinically oriented papers and should therefore be a useful source of ideas, techniques and references for biochemists, physiologists, pharmacologists and neuropsychia­tristi.

viii PREFACE

We would like to express our gratitude to the members of the Scientific Committee and particularly to Dr. Whittaker, who gave valuable suggestions for the choice of the participants and the arrangement of the program, to the local committee to whom the par­ticipants owe the perfect organization of the meeting.

We are particularly grateful to Mrs. Flo Comes for her unique expertise and patience in editing the manuscripts and preparing them in the final form.

Last but not least we want to acknowledge the generous finan­cial support of the Consiglio Nazionale delle Ricerche and of Fidia Research Laboratories which made the meeting possible.

Giancarlo Pepeu Florence

November 1980

Herbert Ladinsky Milan

CONTENTS

DEVELOPMENTAL AND PHYLOGENETIC ASPECTS OF THE CHOLINERGIC NEURONE

ACETYLCHOLINE BIOSYNTHESIS IN DEVELOPING CHOLINERGIC SYNAPSES

E. Giacobini & M. Marchi

AGING OF CHOLINERGIC SYNAPSES IN THE PERIPHERAL AUTONOMIC NERVOUS SYSTEM

M. Marchi & E. Giacobini

THE CHEMICAL EMBRYOLOGY OF THE ELECTROMOTOR SYSTEM OF TORPEDO MARMORATA

W.D. Krenz, T. Tashiro, K. Wachtler, V.P. Whittaker & V. Witzmann

THE REGIONAL DISTRIBUTION OF ACETYLCHOLINE,CHOLIN­ACETYLTRANSFERASE, AND ACETYLCHOLINESTERASE IN VERTEBRATE BRAINS OF DIFFERENT PHYLOGENETIC LEVELS

K. Wachtler

CHOLINE UPTAKE AND CHOLINE ACETYL TRANSFERASE IN BRAIN OF DEVELOPING RATS MADE HYPOTHYROID WITH PROPYL­THIOURACIL

R.N. Kalaria, A.M. Kotas, A.K. Prince, R. Reynolds

1

25

47

59

& P.T.H. Wong 73

MORPHOLOGICAL ANALYSIS OF CHICK EMBRYO HEART DEVELOPMENT

L. Sisto-Daneo & G. Filogamo

ix

85

x

PLACENTAL CHOLINE ACETYLTRANSFERASE PURIFICATION AND PROPERTIES

C. Froissart & R. Massare11i

CONTENTS

91

PERIPHERAL CHOLINERGIC SYNAPSES: GANGLIA

THE RELATIONSHIP BETWEEN CHOLINE UPTAKE AND ACETYLCHOLINE SYNTHESIS IN A SYMPATHETIC GANGLION

B. Collier & S. 0' Regan

MULTIPLE MECHANISMS IN GANGLIONIC TRANSMISSION

N.J. Dun & A.G. Karczmar

PGE1-INDUCED cAMP BIOSYNTHESIS IN THE SUPERIOR CERVICAL GANGLION OF DIFFERENT ANIMAL SPECIES

V. Perri, O. Be11uzzi, C. Biondi, P.G. Borasio,

97

109

A. Capuzzo, M.E. Ferretti & A. Trevisani 119

QUESTIONS RAISED BY THE ELECTRON MICROCOPIC LOCALIZATION OF ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE IN NORMAL AND DENERVATED SUPERIOR CERVICAL GANGLIA IN THE CAT

G.B. Koelle, R. Davis, W.A. Koelle, G.A. Ruch, K.K. Rickard & U.J. Sanville 127

ACETYLCHOLINE METABOLISM IN PC12, A CLONAL CELL LINE ON SECRETORY CELLS

B.D. Howard & W.P. Me1ega

REGULATION OF CHOLINERGIC TRANSMISSION IN ADRENAL HEDULLA

E. Costa, A. Guidotti, I. Hanbauer, T. Hexum, L. Saiani & H.~Y. T. Yang

EFFECT OF LATRODECTUS MACTANS TREDECIMGUTTATUS VENOM ON SYNAPTIC TRANSMISSION OF CHICKEN CILIARY GANGLION IN VITRO

L. Bo1zoni, A. Meneguz & P. Paggi

133

143

155

CONTENTS

PERIPHERAL CHOLINERGIC SYNAPSES: HEART, MYENTERIC PLEXUS AND NEUROMUSCULAR FUNCTION

REGULATION OF ACETYLCHOLINE SYNTHESIS AND RELEASE IN THE ISOLATED HEART

K. Loffelholz, R. Lindmar & W. Weide

MODULATION BY SCOPOLAMINE, ACETYLCHOLINE AND CHOLINE OF THE EVOKED RELEASE OF ACETYLCHOLINE FROM THE GUINEA PIG MYENTERIC PLEXUS: EVIDENCE FOR A MUSCARINIC FEEDBACK INHIBITION OF ACETYLCHOLINE SECRETION

H. Kilbinger, R. Kruel & I. Wessler

KINETIC STUDIES ON THE RELEASE OF [3H]-ACETYLCHOLINE FROM GUINEA PIG MYENTERIC PLEXUS: DIFFERENCE IN THE EFFECTS OF MORPHINE AND REDUCED CALCIUM INFLUX

J.C. Szerb

Na+-K+-ACTIVATED ATPase AND NON-QUANTAL/CYTOPLASMIC RELEASE OF ACETYLCHOLINE

E.S. Vizi

HYDROLYSIS OF ACETYLCHOLINE BY FROG SKELETAL MUSCLE

R. Miledi, P.C. Molenaar & R.L. Polak

EARLY EFFECTS OF DENERVATION ON ACETYLCHOLINE A~~ CHOLINE ACETYLTRANSFERASE IN SKELETAL MUSCLE

R. Miledi, P.C. Molenaar & R.L. Polak

RELEASE OF ACETYLCHOLINE TRIGGERED BY THE VENOM OF GLYCERA CONVOLUTA

R. Manaranche, M. Thieffry & M. Israel

ELECTROPHYSIOLOGICAL AND MORPHOLOGICAL CORRELATES OF THE RE-INNERVATION OF RAT NEUROMUSCULAR JUNCTION: IMPLICATIONS ON THE ROLE OF MEMBRANE COMPONENTS SUCH AS GANGLIOSIDES IN THE MOTOR NERVE SPROUTING

A. Gorio, G. Carmignoto, M. Finesso, A. Leon, P. Marini, L. Tredese & R. Zanoni

xi

159

169

177

187

197

205

215

221

xii CONTENTS

ISOLATION OF SYNAPTIC VESICLES FROM THE MYENTERIC PLEXUS OF GUINEA PIG

G.H.C. Dowe, H. Kilbinger & V.P. Whittaker

PERIPHERAL CHOLINERGIC SYNAPSE: PRESYNAPTIC MECHANISMS

THE STRUCTURE OF CHOLINERGIC SYNAPTIC VESICLES

H. Stadler

INHIBITION OF MEMBRANE TRANSPORT SYSTEMS IN SYNAPTO­SOMES FROM TORPEDO ELECTRIC ORGAN BY SNAKE NEUROTOXINS

M.J. Dowdall & P. Fretten

BIOCHEMICAL AND BIOPHYSICAL ASPECTS OF STIMULATION INDUCED VESICLE HETEROGENEITY IN CHOLINERGIC SYNAPTIC VESICLES

P.E. Giompres, H. Zimmermann & V.P. Whittaker

ACETYLCHOLINE STORAGE AND CALCIUM CLEARANCE BY SYNAPTIC VESICLES

M. Israel

ACETYLCHOLINE CHANGES DURING TRANSMISSION OF A SINGLE NERVE IMPULSE

Y. Dunant, J. Corthay, L. Eder & F. Loctin

UPTAKE OF ACETYLCHOLINE INTO TORPEDO SYNAPTIC VESICLES IN VITRO

Y.A. Luqmani & P. Giompres

A VESICULAR SITE OF ORIGIN FOR THE RELEASE OF A CHOLINERGIC FALSE TRANSMITTER AT THE TORPEDO SYNAPSE

Y.A. Luqmani & V. P. Whittaker

TRANSMEMBRANE POTENTIAL AND CATION DIFFUSION GRADIENTS IN ISOLATED CHOLINERGIC SYNAPTIC VESICLES: POSSIBLE MODEL FOR ENERGIZATION OF VESICULAR ACETYLCHOLINE UPTAKE

J.B. Suszkiw

235

241

249

261

273

287

301

307

313

CONTENTS

INCORPORATION OF ACETATE INTO ACETYLCHOLINE AND OTHER COMPOUNDS IN THE TORPEDO ELECTRIC ORGAN

J. Corthay, F. Loctin & Y. Dunant

PERIPHERAL CHOLINERGIC SYNAPSE: POSTSYNAPTIC ASPECTS

CHOLINERGIC RECEPTOR ISOLATION

xiii

321

W.H. Hopff, A.A. Hofmann, G. Riggio & P.G. Waser 323

NEW EVIDENCE FOR TRUE IMMUNOPHARMACOLOGIC BLOCKADE IN MYASTHENIA GRAVIS

A.K. Lefvert, S. Cuenoud & B.W. Fu1pius

IMMUNOHISTOCHEMICAL DEMONSTRATION OF IgG AND Fab FRAGMENTS AT MOTOR ENDPLATES OF PASSIVELY TRANSFERRED MICE

B. Lowenad1er, E. Hei1bronn & K. Toyka

ON THE EFFECTS OF ANTICHOLINERGIC AGENTS ON MUSCARINIC RECEPTORS OF DIFFERENT LOCALIZATION

D.A. Kharkevich, A.P. Sko1dinov, D.N. Samoi1ov

333

343

& V.A. Shorr 351

PERIPHERAL CHOLINERGIC SYNAPSE: AXONAL ASPECTS

LIGAND INTERACTIONS OF AXONAL MEMBRANES

H.C. Mautner, J.E. Jumb1att & J.K. Marquis

AXONAL TRANSPORT OF PHOSPHOGLYCERIDES TO CHOLINERGIC SYNAPSES

B. Droz, M. Brunetti, L. di Giamberardino, H.L. Koenig & G. Porce11ati

ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE: SIMILARITIES IN NORMAL AND DENERVATED MUSCLES, DIFFERENCES IN AXONAL TRANSPORT

L. di Giamberardino .& J. Y. Couraud

367

377

387

xiv CONTENTS

CENTRAL CHOLINERGIC SYNAPSE: PRECURSORS FOR ACETYLCHOLINE SYNTHESIS

THE ACTIVITY OF GLYCEROPHOSPHOCHOLINE PHOSPHODI­ESTERASE IN BRAIN TISSUE

G.B. Ansell & S. Spanner

SYNTHESIS OF CHOLINE IN THE BRAIN

H. Kewitz & O. P1eu1

ORIGIN OF ACETYL GROUPS OF ACETYLCHOLINE IN THE BRAIN AND THE ROLE OF ACETYLCOENZYME A IN THE CONTROL OF ITS SYNTHESIS

S. Tucek, V. Dolezal & J. Ricny

CHOLINE AVAILABILITY AND THE SYNTHESIS OF ACETYLCHOLINE

D.R. Haubrich, N.H. Gerber, A.B. Pflueger & W.J. Pouch

ACETYLCHOLINE SYNTHESIS AND GLUCOSE OXIDATION WITH VARIOUS OXYGEN ~EVELS IN VIVO AND IN VITRO

G.E. Gibson, H.J. Ksiezak & T.E. Duffy

REGULATION OF ACETYLCHOLINE RELEASE DURING INCREASED NEURONAL ACTIVITY

L. Wecker & A.M. Goldberg

THE UPTAKE AND ACETYLATION OF 3H-CHOLINE IN BRAIN OF INBRED STRAINS OF MICE

R. Reynolds & A.K. Prince

LEAST SQUARES ANALYSES OF THE KINETICS OF CHOLINE UPTAKE IN RAT BRAIN SYNAPTOSOMES

A.M. Kotas & A.K. Prince

393

405

415

425

443

451

463

469

CONTENTS

CENTRAL CHOLINERGIC SYNAPSE: SYNAPTOSOMES AND BRAIN SLICES

INFLUX AND EFFLUX OF N.N.N-TRIMETHYL-N-PROP-2-YNYLAMMONIUM BY A RAT BRAIN SYNAPTOSOME PREPARATION

L.A. Barker

INTERACTION OF CHOLINE TRANSPORT WITH ACETYLCHOLINE RELEASE AND SYNTHESIS

R.M. Marchbanks

CHOLINE TRANSPORT AND THE REGULATION OF ACETYLCHOLINE SYNTHESIS IN SYNAPTOSOMES

R.S. Jope & D.J. Jenden

CHOLINE UPTAKE IN NERVE CULTURES AND IN SYNAPTOSOMAL PREPARATION IS REGULATED BY THE ENDOGENOUS POOL OF CHOLINE

R. Massarelli & T.Y. Wong

INTERRELATIONSHIP BETWEEN ACETYLCHOLINE RELEASE FROM SYNAPTOSOMES AND Na-K ATPase ACTIVITY

J.R. Cooper & E.M. Meyer

ACETYLCHOLINE METABOLISM IN RAT NEOSTRIATAL SLICES

xv

475

489

497

511

521

M.H. Weiler, D.J. Jenden. I.J. Bak & U. Misgeld 531

CENTRAL CHOLINERGIC SYNAPSE: CHOLINERGIC MECHANISMS IN THE EYE

THE CHOLINERGIC SYSTEMS OF THE EYE

T.W. Mittag

LIGHT EVOKED RELEASE OF ACETYLCHOLINE FROM THE RABBIT RETINA IN VIVO

M.J. Neal & S.C. Massey

BIOCHEMICAL AND PUPILLOGRAPHIC STUDIES OF GUINEA PIG IRIS DURING ACETYLCHOLINESTERASE INHIBITION

F. Fonnurn, N.E. S~li, P.K. Opstad, M. Opsahl & R. Lund-Karlsen

541

555

569

xvi CONTENTS

ACETYLCHOLINE RECEPTORS IN THE CENTRAL NERVOUS SYSTEM

ON THE IONIC MECHANISM OF PRESYNAPTIC MUSCARINIC RECEPTOR ACTION IN RAT HIPPOCAMPUS

O. Nordstrom, A. West1ind, B. Hedlund, A. Unden & T. Bartfai 579

MUSCARINIC CHOLINERGIC RECEPTOR LOCALIZATION BY RADIOHISTOCHEMISTRY

J.K. Wamsley, M.A. Zarbin, N.J.M. Birdsall & M.J. Kuhar

"BINDING STATES" OF MUSCARINIC RECEPTORS

N.J.M. Birdsall, C.P. Berrie, A.S.V. Burgen, R. Hammer, E.C. Hulme & J. Stockton

INVESTIGATION ON THE EFFECT OF CHOLINERGIC AGONISTS AND ANTAGONISTS ON CYCLIC NUCLEOTIDE LEVELS IN VIVO: EFFECT OF LYSO-PHOSPHATIDYLSERINE

S. Teo1ato, G. Ca1derini, A.C. Bonetti, A. Battiste11a & G. Toffano

REGULATION OF MUSCARINIC RECEPTOR BINDING

F.J. Ehlert, W.R. Roeske & H.I. Yamamura

STRUCTURAL AND STERIC ASPECTS OF COMPOUNDS RELATED TO OXOTREMORINE

R. Dah1bom

SEARCH FOR NICOTINE-LIKE RECEPTOR BINDING SITES IN BRAIN

A. Nordberg & C. Larsson

IONIC EFFECTS ON ANTAGONIST BINDING TO THE MUSCARINIC RECEPTOR

B. Hedlund

STUDIES ON THE STRUCTURE OF ACETYLCHOLINE RECEPTOR

V,. Witzemann & J .H. Walker

587

595

601

609

621

639

647

653

xvii CONTENTS

NEWLY SYNTHESIZED ACETYLCHOLINE RECEPTOR IN DENERVATED SKELETAL MUSCLE

M.G. Giacobini-Robecchi & M. Garelli

CENTRAL CHOLINERGIC PATHWAYS

ANATOMICAL ORGANIZATION OF SOME CHOLINERGIC SYSTEMS IN THE MAMMALIAN FOREBRAIN

H.C. Fibiger & J. Lehmann

CHOLINERGIC PATHWAYS TO THE CEREBRAL CORTEX IN RATS

H. Wenk, V. Bigl, U. Meyer & D. Biesold

LESIONS OF THE GLOBUS PALLIDUS: CHANGES IN CORTICAL CHOLINE ACETYL TRANSFERASE , CHOLINE UPTAKE AND ACETYL­CHOLINE OUTPUT IN THE RAT

F. Casamenti, F. Pedata, S. Sorbi, G. Lo Conte

659

663

673

& G. Pepeu 685

MAPPING OF CHOLINERGIC SYSTEMS IN ROSTRAL FOREBRAIN OF THE RODENT

H. Kimura, P.L. McGeer, J.H. Peng & E.G. McGeer 695

INTERACTIONS BETWEEN DIFFERENT NEUROTRANSMITTER SYSTEMS

REGULATION OF SEPTAL-HIPPOCAMPAL CHOLINERGIC NEURONS BY CATECHOLAMINES

S.E. Robinson, D.L. Cheney & E. Costa

INTERACTIONS OF NEUROPEPTIDES WITH CHOLINERGIC SEPTAL­HIPPOCAMPAL PATHWAY: INDICATION FOR A POSSIBLE TRANS-SYNAPTIC REGULATION

P.L. Wood, D.L. Cheney & E. Costa

CHOLINERGIC-MONOAMINERGIC INTERACTIONS IN SELECTED REGIONS OF THE BRAIN: HISTOCHEMICAL AND PHARMACOLOGIC ANALYSES

L.L. Butcher, N.J. Woolf, A. Albanese & S.H. Butcher

705

715

723

xviii CONTENTS

ON MODULATION OF CEREBRAL CHOLINERGIC MECHANISMS BY ENDOGENOUS INDOLEAMINES AND THEIR DERIVATIVES

B. Oderfe1d-Nowak & M.H. Aprison

INFLUENCE OF GABA ON ACETYLCHOLINE RELEASE FROM THE GUINEA PIG BRAIN

L. Beani, C. Bianchi & S. Tangane11i

GABA-ACETYLCHOLINE INTERACTION IN THE RAT STRAITUM

B. Scatton & G. Bartho1ini

REGULATION OF CHOLINERGIC ACTIVITY IN THE RAT HIPPO­CAMPUS: IN VIVO EFFECTS OF OXOTREMORINE AND FENFLURAMINE

H. Ladinsky, S. Consolo, A.S. Tire11i, G.L. For1oni

739

763

771

& M. Segal 781

ACETYLCHOLINE, BEHAVIOR AND DRUGS

ACETYLCHOLINE INDUCED ANTINOCICEPTION: COMPARISONS TO OPIATE ANALGESIA

N.W. Pedigo & W.L. Dewey

CHRONIC BARBITAL TREATMENT AND CHOLINERGIC MECHANISMS IN BRAIN

A. Nordberg & G. Wahlstrom

INTERACTION BETWEEN ATROPINE AND HEXOBARBITAL IN THE ABSTINENCE AFTER CHRONIC BARBITAL TREATMENTS IN THE RAT

G. Wahlstrom & A. Nordberg

MARIJUANA AND CHOLINERGIC DYNAMICS

D.L. Cheney, A.V. Revue1ta & E. Costa

ANTINOCICEPTIVE ACTION OF CHOLINOMIMETICS EVALUATED WITH THE METHOD OF THE RETURN OF CORNEAL ANESTHESIA INDUCED WITH PROCAINE

F. Aloisi, A. Scotti de Caro1is & V.G. Longo

795

809

819

825

833

CONTENTS

DO GANGLIOSIDES AFFECT THE RECOVERY OF CHOLINERGIC ENZYMES OF RATS AFTER SEPTAL LESIONS?

M. Wojcik & J. Ulas

COMPARA~IVE STUDIES ON RAT BRAIN SOLUBLE ACETYL­CHOLINESTERASE AND ITS MOLECULAR FORMS DURING INTOXICATION BY DFP AND PARAOXON

H. Michalek, G.M. Bisso & A. Meneguz

CLINICAL SIGNIFICANCE OF CHOLINERGIC MECHANISMS

BASIC PHENOMENA UNDERLYING NOVEL USE OF CHOLINERGIC AGENTS, 'ANTICHOLINESTERASES AND PRECURSORS IN NEUROLOGICAL INCLUDING PERIPHERAL AND PSYCHIATRIC DISEASE

A.G. Karczmar

CLINICAL TRIALS WITH CHOLINE AND 4-AMINOPYRIDINE IN HUNTINGTON'S CHOREA

S.M. Aquilonius & S.A. Eckernas

PHARMACOKINETICS OF NEOSTIGMINE AND PYRIDOSTIGMINE IN MAN AND ITS CORRELATION TO CLINICAL EFFECTS IN MYASTHENIA GRAVIS

S~A. Eckernas, S.M. Aquilonius, P. Hartvig, B. Lindstrom, P.O. Osterman & E. Stalberg

RED BLOOD CELL/PLASMA CHOLINE RATIO - A POSSIBLE BIOLOGICAL MARKER OF LITHIUM THERAPY - CLINICAL CORRELATIONS AND LIMITATIONS

E.F. Domino, B. Mathews, S.K. Tait, S.K. Demetriou

xix

841

847

853

871

879

& F. Fucek 891

BLOOD CHOLINE AND ITS MEANING IN PSYCHIATRIC AND NEUROLOGIC DISEASE STATES

I. Hanin, D.G. Spiker, A.G. Mallinger, U. Kopp, J.M. Himmelhoch, J.F. Neil & D.J. Kupfer 901

CHOLINERGIC DYSFUNCTION: A COMMON DENOMINATOR IN METABOLIC ENCEPHALOPATHIES

J.P. Blass, G.E. Gibson, T.E. Duffy & F. Plum 921

xx CONTENTS

CHOLINOMIMETIC AGENTS AND HUMAN MEMORY: PRELIMINARY OBSERVATIONS IN ALZHEIMER'S DISEASE

K.L. Davis, R.C. Mohs, B.M. Davis, G.S. Rosenberg, T.H. Horvath & Y. DeNigris 929

EFFECTS OF LECITHIN ON MEMORY AND PLASMA CHOLINE LEVELS: A STUDY IN NORMAL VOLUNTEERS

J.C. Gillin, N Sitaram, H. Weingartner, C. Crammer & I. Hanin

HYPERSENSITIVE CHOLINERGIC FUNCTIONING IN PRIMARY AFFECTIVE ILLNESS

N. Sitaram, A.M. Moore, C. Vanskiver, J. Blendy,

937

J.I. Nurnberger, Jr., E.S. Gershon & J.C. Gillin 947

PARTICIPANT LIST 963

CONTRIBUTOR INDEX 973

SUBJECT INDEX 977