Table Of ContentBasic and Clinical Aspects of Neuroscience
Edited by E. Fluckiger (Managing Editor),
o.
E. E. Muller and M. Thorner
A
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Springer Sandoz
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Advanced Texts
SANDOZ
The Dopaminergic System
With Contributions by
B. Halasz K. Fuxe L. F. Agnati M. Kalia
M. Goldstein K. Andersson A. Harfstrand B. Clark
With 23 Figures
Springer-Verlag Berlin Heidelberg New York Tokyo
Professor Dr. Edward Fluckiger
Pharmazeutische Abteilung
Praklinische Forschung
SandozAG
CH-4002 Basel
Professor Dr. Eugenio E. Muller Professor Dr. M. O. Thorner
Dipartimento di Farmacologia Dept. of Internal Medicine
Facolta' di Medicina e Chirurgia School of Medicine
Universita' degli Studi di Milano University of Virginia
Via Vanvitelli, 32 Charlottesville, Virginia 22908
1-20129 Milano USA
ISBN-13:978-3-540-13700-9 e-ISBN-13:978-3-642-69948-1
DOl: 10.1007/978-3-642-69948-1
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Preface
This new series of Advanced Texts on
"Basic and Clinical Aspects of Neuroscience" is a joint undertaking by Springer
Verlag and Sandoz Ltd. The series is designed to keep general practitioners and
clinicians, as well as medical biologists and advanced students in medicine or
biology, informed of the current state of knowledge in certain areas of neuro
science.
Each volume of the series is devoted to one topic and contains contributions by
acknowledged authorities in their field. The authors are chosen not only for their
expertise but also for their ability to convey their knowledge in a clear and
straightforward manner, intelligible to the nonspecialist. Great emphasis is given
to the illustrations, which are designed to enhance comprehension of the text.
The series is fortunate in having as editors Prof. E. E. Muller (Milan) and Prof.
M. O. Thorner (Charlottesville), both for the planning of the program and for the
contributions.
Basle, June 1985 E. Fluckiger
Managing editor
Table of Contents
Introduction to Neuroendocrinology
B.HALAsz
Oxytocin- and Vasopressin-Producing Neurons . . . . . . . . . . . .. 1
Pituitary Trophic Hormone Releasing and Release Inhibiting Factors
(Hormones) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3
Anterior Pituitary Hormones, Gastrointestinal Hormones, and Other
Peptides in the Central Nervous System .............. 5
Monoaminergic Systems . . . . . . . . . . . . . . . . . . . . . . . 6
Structural Organization of the Nervous Elements Involved in the
Control of the Pituitary. . . . . . . . . . . . . . . 7
Peripheral Innervation of the Endocrine Glands . 8
References ..................... 8
Dopaminergic Systems in the Brain and Pituitary
K. FUXE, L. F. AGNA n, M. KALlA, M. GOLDSTEIN, K. ANDERSSON,
and A. HARFSTRAND
Ascending DA Neuron Systems. . . . . . . . . . . . . . . . . . . . 11
Descending DA Neuron Systems . . . . . . . . . . . . . . . . . . . 16
Local DA Neuron Systems of the Midbrain, Hypothalamus, and the
Preoptic Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 16
Local DA Neurons of the Olfactory and Optic System. . . . . . . . . 18
Studies on the Postsynaptic Regulation of DA Mechanisms: Evidence
for Receptor-Receptor Interactions at the Local Circuit Level and at the
Comodulator Level. . . . . . . . . . . . . . . . . . . . . . . . . . 18
On the Functional Role of the Nigrostriatal and Mesolimbic DA
Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Mesolimbic and Mesolimbocortical DA Neurons and Their Possible
Functional Role .......................... 21
Tuberoinfundibular DA Neurons and Their Role in Regulating
Secretion of Hormones from the Anterior Pituitary Gland ... 21
Tuberohypophyseal DA Neuron Systems and Their Role in Regulating
Secretion of Hormones from the Pars Intermedia of the Anterior
Pituitary Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Hypothalamic DA Neuron Systems and Their Role in Regulating
Secretion of Hormones from the Posterior Pituitary Gland 23
References ............................... 24
VIII Table of Contents
The Role of Dopamine in the Periphery
BARBARA 1. CLARK
Introduction ............ . 27
Cardiovascular Effects of Dopamine 28
Vascular Receptors . 30
Sodium Excretion ......... . 32
Renin Secretion. . . . . . . . . . . . 32
Effects on Ganglionic Transmission. 32
Prejunctional Receptors 33
Dopaminergic Nerves 36
Conclusion 38
References ..... . 38
Introduction to Neuroendocrinology
Bela Halasz
2nd Department ofA natomy, Semmelweis University Medical School, Tiizoltb utca 58,1094 Budapest IX, Hungary
In recent decades very spectacular progress has been made of the smooth muscles of the uterus and breast, and for an
in the field of neuroendocrinology. We gained a vast tidiuresis.
amount of important new information which in essence The application of immunocytochemical and radioim
confirmed and proved the original basic concepts of the munoassay techniques to the study of the distribution of
discipline; however, it also led to a significant revision of oxytocin and vasopressin has confirmed the original con
our views about neuroendocrinology in general and about cept but, in addition, it has revealed the presence of both
some of its special areas in particular. Forty years ago neu peptides throughout the central nervous system (Fig. 1).
roendocrinology meant primarily neurosecretion as a pe Vasopressin- and oxytocin-containing neurons which do
culiar phenomenon, the supraoptico- and paraventriculo not appear to project to the posterior pituitary have recent
hypophyseal system producing vasopressin and oxytocin, ly been identified both inside and outside the hypothala
and the neural control of the anterior pituitary gland. mus. Such vasopressin neurons were found, for example,
Nowadays the discipline covers much more. It deals with in the hypothalamic suprachiasmatic nucleus, septal re
all interactions between hormones and nerve structures. gion, amygdala, and region of the locus ceruleus. Many
There are an infinite number of such interactions, which oxytocin and some vasopressin neurons of the paraventri
exist at very different levels. Therefore, it is almost impos cular nucleus give rise to projections to the brainstem and
sible to draw boundaries of the discipline and to give a spinal cord (for references see [13]). There is an extensive
more detailed definition. network of vasopressin and oxytocin fibers distributed
As is often true in science, improvements in research throughout the mammalian central nervous system. The
tools have contributed greatly to the progress mentioned areas containing such fibers range from autonomic centers
above. Refined techniques have been introduced for chem or areas involved in nociception in the brainstem and spi
ical characterization and synthesis of peptides. Immuno nal cord to forebrain limbic structures, and even to neocor
logical techniques, both radioimmunoassays and immuno tex. Synapses in which the vasopressin- or oxytocin-con
cytological methods, became available to measure minute taining nerve terminal is the presynaptic structure have
quantities of hormones and neurohormones, and to identi been observed. Some of the projections of vasopressin or
fy and localize various peptidergic elements and other sub oxytocin neurons are already established.
stances. New tract-tracing methods have been worked out The question arises: What are the functions of oxytocin
for detailed analysis of neuronal connections. New phar and vasopressin in the central nervous system? There is
macologic research tools have also been developed. experimental evidence that both hormones are involved in
Some of the main findings obtained in the last decades various brain functions. Behavioral effects of administered
and greatly influencing the present picture of neuroendo oxytocin and vasopressin have been observed, in particu
crinology are briefly summarized on the following pages. lar their effects on memory and learning. There are also re
ports about other actions of these hormones (antipyretic,
analgesic, etc.). Vasopressin may playa role in cardiovas
cular regulation through central pathways. Further, there is
Oxytocin- and Vasopressin-Producing Neurons evidence that both vasopressin and oxytocin can alter the
electrical activity of neurons or the catecholamine turnover
in specific brain areas, or can influence cAMP production.
Until the 1970s oxytocin and vasopressin were thought of Thus, oxytocin and vasopressin, originally character
primarily as hormones of the posterior pituitary, produced ized as posterior pituitary hormones, appear to have an ad
by the neurons of the paraventricular and the supraoptic ditional important role in influencing the activity of neu
nucleus and released into the blood vessels of the neural rons through direct projections to these elements and
lobe. This so-called paraventriculo- and supraopticohypo hence may play an important part in a variety of central
physeal tract was considered as a well-defined, distinct sys nervous system functions.
tem producing the hormones responsible for contraction
Basic and Clinical Aspects of Neuroscience
Springer-Sandoz Advanced Texts
© by Springer-Verlag Berlin· Heidelberg 1985
2 Bela Halasz
CCALL
o
o 0
o
000
MedUlla
oblongata
o
Vasopressin Perikarya
t3
Vasopressin Fibres and terminals
o
Oxytocin Perikarya
t3
Oxytocin Fibres and terminals
Introduction to Neuroendocrinology 3
Fig.2. Schematic illustration of
the structural basis oft he
neurohumoral mechanism
controlling the anterior pituitary
Neurons producing
the hypophysiotrophic
neurohormones
Adenohypophysis
Pituitary Trophic Hormone Releasing and Release physeal portal vascular system by which they are carried to
Inhibiting Factors (Hormones) the cells of the adenohypophysis (Fig.2). This hypothesis
has been proved in the last two decades. Several peptides
called have been isolated from the hypothalamus, chemi
In 1947 Green and Harris [6] formulated the concept that cally identified, and synthesized: a tripeptide [called thyro
neural control of the anterior pituitary is exerted by a neu tropin releasing hormone (TRH)] causing release of the
rohumoral mechanism, i. e., the central nervous system thyroid-stimulating hormone (TSH), a decapeptide [called
synthesizes "hypophysiotrophic" substances which are re luteinizing hormone releasing hormone (LHRH), gonado
leased from the nerve terminals in the hypothalamic medi lib erin, or luliberin] with releasing activity for the luteiniz
an eminence and pituitary stalk and they enter the hypo- ing hormone (LH) and the follicle-stimulating hormone
(FSH), a tetradecapeptide [named somatostatin, growth
hormone inhibiting factor or somatotropin release inhib
~r------------------------------------ iting factor, (SRIF)] inhibiting the release of growth hor
Fig. 1. Distribution of vasopressin and oxytocin immunoreactive
mone and TSH (for references see [14]), and a peptide con
neuronal elements in the central nervous system. CCALL, corpus
callosum taining 41 amino acids [corticotropin releasing factor
4 Bela Halasz
Telencephalon
Diencephalon
o
SRIF Perikarya
£3
SRIF Fibers and terminals
o
CRF Perikarya
t3
CRF Fibres and terminals
OT Hypoth.
Mesencephalon
Spinal cord
