5-Hydroxytryptamine and Related Indolealkylamines

946 Pages·1966·41.87 MB·English

by  Maffo Vialli (auth.), Vittorio Erspamer (eds.)

Handbuch der
experimentellen Pharmakologie
Handbook of
Experimental Pharmacology
Heffter-Heubner New Series
Herausgegeben von I Edited by
O. Eichler A. Farah
Heidelberg Syracuse, N. Y.
Beirat I Advisory Board
J.
G. Acheson· E. Ariens . Z. M. Bacq . F. von Briicke . V. Erspamer
W. Feldberg. R. Furchgott . A. Goldstein· G. B. Koelle
O. Krayer . K. Repke . M. Rocha e Silva· P. Waser
Vol. XIX
Springer-Verlag· Berlin· Heidelberg. New York 1966
5-Hydroxytryptamine
and Related Indolealkylamines
Contributors
H. Blaschko . W. P. Burkard· A. Carlsson· L. H. Cohen· V. Erspamer
K. F. Gey . L. Gyermek. P. B. Hagen. A. Hanson· W. G. Levine
P. Mantegazzini . A. Pletscher . R. S. Stacey. M. Vialli
Sub-Editor
Vittorio Erspamer
With 109 Figures and 2 Plates
Springer-Verlag New York Inc. 1966
ISBN 978-3-642-85469-9 ISBN 978-3-642-85467-5 (eBook)
001 10.1007/978-3-642-85467-5
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Titel·Nr. 5724
Preface
The study of biogenic amines, which from the beginning of modern pharma
cology has always attracted the enthusiastic attention of research workers and has
led to some of the most brilliant and illuminating experimental results in biology,
has been unexpectedly extended in the last fifteen years. 'With the discovery of
5.hydroxytryptamine (enteramine, serotonin), in fact, the vast field of indole
alkylamines has been opened up for research.
In a decade of intensive and dedicated work, an immense amount of experi
mental data has been collected, the significance of which, having rapidly overrun
the limits of pharmacology, physiology, and biochemistry, has spread into all
fields of biology and medicine, as previously occurred with choline esters, catechol
amines and imidazolealkylamines. Thus, the study of indolealkylamines, espe
cially that of their metabolism, has led not only to explanation of the mechanism
of action, formerly largely obscure, of some important drugs, to clarification of
the pathogenesis of some morbid syndromes and to a parallel flourishing of
research on other biogenic amines, but also to surprising achievements in the
field of therapeutics. The discovery of monoamineoxidase and dopadecarboxylase
inhibitors, and of drugs which block the storage of biogenic amines in the body
depots are among the most striking results of research on the indolealkylamines.
The present volume of the "Erganzungswerk" attempts to offer the reader the
best of about 4000 papers which have appeared in the field of the indolealkyl
amines up till the end of 1963. Many of the data reported in the volume can
already be considered to be firmly established; others still require confirmation.
Some of the problems herein posed can be considered solved, while others need
elucidation by future research. First and foremost among these is the problem
of the biological significance of 5-hydroxytryptamine and related indolealkyl
amines in their various localizations. It will be an adequate reward for our
efforts and those of our collaborators if this volume proves to be of even little
help towards research progress in this field of endeavour, to which each of us has
dedicated some of his best years.
I should like to express my gratitude to Prof. OSKAR EICHLER for the testi
mony of esteem he as shown me in selecting me as Sub-Editor of this volume and
my warmest thanks to all the collaborators who have taken a share in the labour
of this enterprise by adding to it the contributions of their exceptional competence.
Thanks are particularly due to Dr. A. HANSON and Dr. L. GYERMEK who agreed
to write their chapters under difficult conditions owing to the late withdrawal of
other collaborators. I also beg to be permitted (since I shall probably never have
another similar opportunity) to thank Professors M. VIALLI and P. DI MATTEI,
who gave me so much encouragement in the study of "enteramine" at a time
when it could certainly not have been said that this study would lead to success or
immediate satisfaction. And finally I should like to thank my dear ones (my wife,
who has also been very helpful to me in the compilation of the bibliography and
the subject index, and my children, Francesco and Maria Luisa) for having made
it possible, by creating a quiet atmosphere in which to work, to carryon even
under conditions that were not always easy. V. ERSPAMER
List of the most usual abbreviations
ACH Acetylcholine 5-HT 5-Hydroxytryptamine
ACTH Adrenocorticotropic hormone 5-HTP 5-Hydroxytryptophan
AMP Adenosine monophosphate 4-HIAA 4-Hydroxyindoleacetic acid
ATP Adenosine triphosphate 4-HT 4-Hydroxytryptamine
BAB I-Benzyl-2-methyl-5-methoxy-N,N 4-HTP 4-Hydroxytryptophan
dimethyltryptamine (benzyl ana 6-HIAA 6-Hydroxyindoleacetic acid
logue of bufotenine) 6-HT 6-Hydroxytryptamine
BAS I-Benzyl-2-methyl-5-methoxy 6-HTP 6-Hydroxytryptophan
tryptamine (benzyl analogue of 7 -HIAA 7 -Hydroxyindoleacetic acid
serotonin) 7-HT 7-Hydroxytryptamine
BOL 2-Bromo-D-Iysergic acid diethyl 7-HTP 7-Hydroxytryptophan
amide IAA Indoleacetic acid
CNS Central nervous system LSD D-Lysergic acid diethylamide
CPZ Chlorpromazine LSM D-Lysergic acid morpholide
DAO Diamine oxidase MAO Monoamine oxydase
DCA Decarboxylase of aromatic L-amino MBL I-Methyl-2-bromo-D-lysergic acid
acids diethylamide
DOCA Desoxycorticosterone acetate MSH Melanocyte-stimulating hormone
DHE Dihydroergotamine NE Norepinephrine, noradrenaline
DMPP 1,1-Dimethyl-4-phenylpiperazinium PIH fJ-Phenylisopropylhydrazine
bromide PAS Paraaminosalicylic acid
DOPA 3,4-Dihydroxyphenylalanine RPF Renal plasma flow
DPN Oxidized diphosphopyridine nucleo STH Somatotropic hormone
tide T Tryptamine
EC Enterochromaffin cell(s) TMA Tetramethylammonium bromide
EDTA Ethylenedinitrile tetraacetic acid TP Tryptophan
tetrasodium salt TPNH Reduced triphosphopyridine
EEG Electroencephalogram nucleotide
GABA y-Aminobutyric acid UML I-Methyl-D-Iysergic acid butanol
GFR Glomerular filtration rate amide, methysergide
5-HIAA 5-Hydroxyindoleacetic acid
List of Contributors
HERMANN BLASCHKO, Dr., Dept. of Pharmacology, University of Oxford, Oxford,
Grcat Britain.
WILLY PAUL BURKARD, Dr. phi!., F. Hoffmann-La-Roche & Co. Ltd., Basel,
~witzerland.
ARVID CARLSSON, Profcssor of Pharmacology, Department of Pharmacology, Uni
versity of G6teborg, G6teborg, Sweden.
LEONARD H. COHEN, PH. D., Associate Member, Institute for Cancer Research,
Fox Chase, Philadelphia, Pa., USA.
VI'J".roRIo ERSPAl\1ER, Professor of Pharmacology, Department of Pharmacology,
University of Parma, Parma, Italy.
KARL li'RIEDRICH GEY, Dr. med., F. Hoffmnnn-La-Roehe & Co. Ltd., Basel,
Switzerland.
LASZLO Gn~RMEK, M. D., Associate Director, Biological Research, Syntex Lnbo
ratories, Palo Alto, California, USA.
PAUL B. HAGEN, Dr., Professor of Biochemistry, Queen's University Kingston,
Ontario, Canada.
ARNE HANSON, Dr., Department of Clinical Chemistry, General Hospital, Malmo,
Sweden.
WALTER, G. LEVINE, Department of Pharmacology, Albert Einstein College of
Medicine, New York 61, N.Y., USA.
PAOLO MANTEGAZZINIt, Dr., Laboratori Ricerehe Farmitalia S. p. A.Milano, Italy.
ALFRED PLETSCHER, Professor Dr. med. et phi!., F. Hoffmann-La-Roche & Co.
Ltd., Basel, Switzerland.
REGINALD STEPHEN STACEY, Professor of Phnrmacology nnd Therapeutics, St.
Thomas's Hospital Medical School, London S.E. 1, Great Britnin.
MAFFO VIALLI, Professor, Direttore dell'Istituto di Anatomia Comparatn dell'
Universita di Pavia e Centro di Studio rer l'Istochimicn dcl C.N.R., Pavin,
Italy.
Contents
Page
(,hapt('r 1. Histology of tile enterocilromaffin c('ll syst('m. By :\1. VIALLI. 'Vith 10 figures
and 2 plates
I. Introduction . . . . . . . . . . . . 1
II. The elements of the enterochromaffin cell system 2
ITI. Histochemical characteristics of 5·HT of diagnostic importance 4
A. Fixability charaderisties 5
B. Colour reactions. . . . 6
1. Chromaffin readion . 7
2. Argentaffin reactions and argentophily 7
3. Diazo reactions. . . . . . . 9
4. Pearse's thvo·indoxvl reaction 10
;3. Other reactions. .". . . . . 10
G. Reactions which do not give the expected positive response 11
7. Various procedures . . . . . . . . . . . 11
C. Fluorescence as a diagnostic criterion 11
D. Limits of histochemical diagnosability of 5-HT 12
E. Histochemical data obtained by destructive extra-situm methods 12
1Y . The enterochromaffin cell system. . . 13
A. Enterochromaffin cells . . . . . . 13
1. The typical enterochromaffin cell 14
a) Specific granules . . . . . . 15
Ot) Histochemical characteristics p. 16. - fJ) Histophysical characteris
tics p. 17. - ,,) Ultrastructural data p. 18. - 0) Data obtained by
homogenization and differential centrifugation p. 19.
b) Topographical distribution . . . . . . . . . . . . 19
Ot) Intestinal distribution p.19. - (3) Extra-intestinal localization p.21.
c) Taxonomical distribution . . . . . . . . . . . . . 22
2. Brief notes on the argentophil pre-enterochromaffin cells. 23
3. Embryology of the enterochromaffin cell. . . . . 25
a) Time of appearance of the enterochromaffin cell 25
b) Experimental embryological data. . . . . . . 26
c) Origin of the enterochromaffin cell . . . . . . 27
4. Various functional conditions of the enterochromaffin cell 28
B. Chromaffin cells of the posterior salivary glands of Octopoda 30
C. Chromaffin cells in the hypobranchial gland of Muricidae 31
D. Cutaneous poison glands in Amphibians 33
E. Chromaffin cells in Calliactis parasitica 35
F. Poison gland cells of some scorpions . 36
G. )Iast cells in the rat and the mouse 37
V. Localizations of phenolic and indolic substances which cannot be referred to a-HT 38
VI. Localizations of 5-HT which cannot be histochemically demonstrated 38
VII. Final considerations. 40
VIII. Technical appendix. . 41
A. Fixations. . . . . 41
1. Formalin fixation 41
2. Freezing drying. 41
3. Fixation for electron-microscopy 42
B. Principal reactions. . . . . . . . 42
1. Chromaffin reactions . . . . . 42
a) Fixation for chromaffin reaction 42
b) Reaction on sections . . . . . 42
x Contents
Page
2. Iodaffin reactions. . . . . . . . . . . . . . . . . 43
3. Silver reactions. . . . . . . . . . . . . . . . . . 43
a) Argentaffin reaction according to MASSON-HAMPERL 43
b) Argentaffin reaction according to MASSON . . . . . 44
c) Methenamine silver argentaffin reaction according to GOMORI-BuRTNER 44
d) Bodian's argyrophil technique . . . . . . . . . . . . . . . . . . . 44
e) Gross-Schultze's modification of Bielchowski's argyrophil technique. . 45
f) Feyrter's adaptation of Gross-Schultze's argyrophil technique to paraffin
embedded sections 46
4. Schmorl's reaction. . . . . . . . . . . . . . . . 46
5. Diazoreactions . . . . . . . . . . . . . . . . . 46
a) Diazoreaction with the diazotate of sulfanilic acid 46
ex) In alkaline solution p. 46. - (J) In acid solution p. 47. - y) In alkaline
solution with subsequent strong acidification p. 47.
b) Diazoreaction with stabilized diazotates. . . . . . . . . . . " 47
c) Coupled tetrazonium reaction according to PEARSE . . . . . " 48
d) Diazosafranin method according to LILLIE, BURTNER and HENSON 48
6. Gibbs's dichloroquinonechlorimide reaction. . . . . . . . . . . .. 48
7. Pearse's thioindoxyl reaction. . . . . . . . . . . . . . . . . .. 48
C. Estimation of the weighted index of granularity in the rat according to GRI-
RINGHELLI and MIRA . 49
References 52
Chapter 2: Chemical analysis of indolealkylamines and related compounds. By A. HANSON.
With 11 figures
Introduction. . . . . . . . . . . . . . . . . . . 66
A. Isolation and fractionation from biological material 66
I. Extraction procedures . . . 67
1. Acetone extraction . . . 67
2. Butanol extraction . . . 67
3. Other solvent extractions. 68
II. Chromatographic procedures 68
1. Adsorption chromatography 68
2. Ion exchange chromatography 69
3. Paper chromatography. . . . 71
4. Molecular sieving (gel filtration) 71
III. Paper electrophoresis. . 72
B. Identification. . . . . . . . 72
I. Ultraviolet absorbancy . 72
II. Fluorescence . . . . 74
III. Colour reactions. . . . 77
I. Aldehyde reactions . 77
2. Xanthydrol reaction. 78
3. I-Nitroso-2-naphthol reaction. 79
4. Diazo reactions. . . . . 79
IV. Countercurrent distribution. 81
V. Paper chromatography. . 82
1. Chromatography paper 82
2. Solvent systems 83
3. Location of spots . . . 86
4. Rt values of indolealkylamines and related compounds 89
5. Quantitative paper chromatography. . . . . . . . 89
VI. Thin layer chromatography. 90
VII. Gas chromatography .... 91
VIII. Paper electrophoresis. . . . 92
C. Quantitative determination of specific compounds. 94
I. Simple indoles 94
I. Tryptamine 94
2. Tryptophan 96
3. Indoleacetic acid 98
Contents XI
Page
II. 5-Hydroxyindoles 98
1. 5-Hydroxytryptamine 99
2. 5-Hydroxytryptophan 103
3. 5.Hydroxyindoleacetic acid 104
References . . . . 107
Chapt!'r 3: Bioassay 01' indoll'alkylamines. By Y. ERSPA:lIER. 'Yith 5 figures.
I. Extraction of 5-HT and related indolealkylamines from tissues and organic fluids 113
IT. Smooth muscle preparations used in the bioassay of indolealkylamines 115
1. Rat uterus . . . . . . . . . 115
a) El'spanwr's original method. lliS
b) Gaddum's teehniglle . 117
2. Rat fundus strip . 117
:{. Rat colon . . . . 1:2<)
cl. Guinea.pig ileulll . I:2il
;3. Isolated rabbit ear 121
o. Molluscan heart 122
a) Yenus mercenaria 122
b) Helix (se\'eral species) 12:3
c) Spisula (~Iactra) solida 124
d) .. \nodonta cygne a 124
e) Other Illolluscs 12;")
7. ~Iisccllaneous preparations. 12;3
Ill. The relatiye potency of natural and synthetic indolealkylamines 126
References . . . . . . . . 129
Challtl'r 4: OceurreJl('e of indolealkyluminl's ill lIutUfl'. By Y. ERSPA:lIER. "'ith 1 figure.
I. Introduction . . . . . . 132
IT. Yertebrates. . . . . . . 132
1. Gastro-intestinal tract 132
2. Blood . . 138
3. Spleen. . . . 141
4. Mast cells. . . 141
5. Other extracerebral tissues of mammals 143
G. Central and peripheral nen'ous system 145
7. Yenom of reptiles . . . 154
8. Amphibian skin. . . . . . . . . . 154
9. Fish tissues and venoms . . . . . . 157
10. "Grine . . . . . . . . . . . . . . 157
11. Biological fluids and liquids other than urine 159
III. Invertebrates 159
IY. Plants. 163
References 166
Chapter i"i: Biosynthesis 01' indolealkylamilles. l)h~'siological release and transport 01'
i"i-hydroxytryptamine. By P. 13. HAGEX and L. H. COHEK. 'With 4 figures.
I. Introduction . . . . . . . . . . . . . . . 182
II. The hydroxylation of tryptophan . . . . . . . . . . . . . . . . . . 184
III. The decarboxylation of 5-hydroxytryptophan. . . . . . . . . . . . . 187
1. The identity of .5-hydroxytryptophan decarboxylase with dopa decarboxylease 187
2. Distribution of i>-hydroxytryptophan decarboxylase (dopa decarboxylase) with-
in the body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
3. Intracellular distribution of 5.hydroxytryptophan decarboxylase (dopa decar-
boxylase) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
4. Pyridoxal phosphate as a coenzyme of 5-hydroxytryptophan decarboxylase
(dopa decarboxylase) .......................... 190
I). Substrate specificity of I).hydroxytryptophan decarboxylase (dopa decarboxy-
lase) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
6. Inhibitors of 5-hyclroxytryptophan decarboxylase (dopa decarboxylase) ... 192
7. StuclieR on I).hydroxytryptoplmn decarboxylase (dopa decarboxylase) in vivo 194
XII Contents
Page
8. Mechanism of the decarboxylase reaction . . . . . . . . . . . . 196
9. Differences in 5.hydroxytryptophan decarboxylase activity with age 198
IV. Biosynthesis of melatonin .... 199
V. Storage of 5-hydroxytryptamine . 200
VI. Turnover of 5-hydroxytryptamine . 202
References . . . . . . . . . . . . . 205
Chapter 6: Metabolism of indolealkylamines. By H. BuscHKo and W. G. LEVINE. With
3 figures.
A. Introduction. . . . . . . . . . . . 212
B. Enzymes acting on indolealkylamines . 212
I. Amine oxidases . . . . . . . . 212
1. The intracellular (and carbonyl.reagent-intensitive) amine oxidase. 212
a) Preparation of amine oxidase .... . 213
b) Intracellular localization of amine oxidase . . . 213
c) Distribution of amine oxidase . . . . . . . . 215
d) Histochemistry of amine oxidase . . . . . . . 218
e) Indolealkylamines as substrates of amine oxidase ...... 219
(X) Tryptamine and 5-hydroxytryptamine p.219. - fl) N-substituded
amines p. 220. - y) Other indolealkylamines p. 220.
2. Amine oxidases inhibited by carbonyl reagents 220
3. Microsomal deaminating enzymes . . . 222
4. Microsomal demethylating enzymes . . 222
II. Reactions of the phenolic hydroxyl groups 222
1. Hydroxyindole oxidases . . . . . . 223
2. Conjugases and dephosphorylase 225
3. Hydroxyindole-O-methyl transferase. . 225
III. Introduction of the phenolic hydroxyl groups 226
IV. Introduction of N-methyl groups. . . . . . 226
V. N-acetylase . . . . . . . . . . . . . . . 227
VI. Oxidative deamination and transamination involving 5.hydroxytryptophan 227
1. Amino-acid oxidases. . 227
2. Transaminases . . . . . . . . . . . . . 228
C. Metabolism of indolealkylamines . . . . . . . . . 228
I. Metabolites arising from deamination reactions . 228
1. Metabolites of tryptamine and of its N-methylated derivatives 228
2. Metabolites of 5-hydroxytryptamine and related amines 229
a) 5-Hydroxytryptamine. . . . . . 229
b) Other 5-hydroxyindolealkylamines 233
c) Derivatives of 5-hydroxyindoles 233
3. 4-Hydroxyindoles . . 233
II. N-Acetylated metabolites. . 234
III. Excretion of O-sulphates . . 234
IV. Excretion of O.glucuronides . 235
V. Formation and excretion of phenolic compounds. 235
VI. Metabolism of melatonin 236
D. Summary 237
References . . . . . . . . . . 239
Chapter 7: Peripheral physiological and pharmacological actions of indolealkylamines. By
V. ERSPAMER. With 16 figures.
I. Acute toxicity of indolealkylamines. . 245
II. Action on the systemic blood pressure . 246
III. Action on special vascular areas 260
1. Coronary vascular bed . 260
2. Pulmonary vessels. . . 260
3. Liver vessels . . . . . 263
4. Spleen vessels 264
5. Vessels of the placenta. 265