Dopamine-Endocrine and Oncogenic Functions

438 Pages·2020·66.759 MB·\438

by  Nira Ben-Jonathan (Author)

Dopamine

Dopamine
Endocrine and Oncogenic
Functions
Nira Ben-Jonathan
First edition published 2020
by CRC Press
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Contents
Preface xi 2.2.5 Specific properties and brain distribution
of D1-like receptors 36
Author xiii
2.2.6 Specific properties and brain distribution
of D2-like receptors 38
Chapter 1 2.2.7 DAR oligomerization, desensitization,
and constitutive activity 40
Homeostasis of Dopamine 1
1.1 INTRODUCTION 1 2.3 CANONICAL VERSUS
NONCANONICAL SIGNALING
1.2 BIOSYNTHETIC ENZYMES 2
BY DAR SUBTYPES 42
1.2.1 Tyrosine hydroxylase 3
2.3.1 The consequences of DAR coupling to
1.2.2 Dopa decarboxylase 5 G proteins 42
1.2.3 Dopamine beta-hydroxylase and 2.3.2 The adenylate cyclase/cAMP/PKA signaling
phenylethanolamine-N-methyltransferase 6 pathway 43
2.3.3 Cross-talk of multiple signaling pathways 44
1.3 METABOLIC ENZYMES 7
2.3.4 Role of the cGMP pathway 45
1.3.1 Monoamine oxidases (MAOs) 8
1.3.2 Catechol-O-methyltransferase 9 2.4 DAR AGONISTS AND ANTAGONISTS 46
1.3.3 Glucuronosyltransferases and sulfotransferases 10 2.4.1 Overview of DAR-selective ligands 46
2.4.2 D2R-altering drugs 47
1.4 MEMBRANE AND VESICULAR
2.4.3 Atypical antipsychotics 48
TRANSPORTERS 12
1.4.1 Transporters of monoamine neurotransmitters 12 2.4.4 Drug selectivity 48
1.4.2 The dopamine transporter 14 2.4.5 Peripheral dopaminergic altering drugs 49
1.4.3 Pharmacology of DAT 15 2.5 DOPAMINE RECEPTOR KNOCKOUT
1.4.4 DAT-deficient mice 16 MICE 50
1.4.5 Vesicular monoamine transporters 16 2.5.1 Phenotypes of individual DAR-KO mice 50
1.4.6 Organic cation transporters and plasma 2.5.2 D2R deletion and pituitary functions 51
membrane monoamine transporters 18
2.6 SYNOPSIS 51
1.5 STORAGE, RELEASE, AND REUPTAKE 19
REFERENCES 52
1.5.1 Functional coupling between DA synthesis
and storage 19
1.5.2 Characteristics of synaptic vs. secretory vesicles 20
1.5.3 Mechanism of exocytosis 22 Chapter 3
Distribution and Characteristics
REFERENCES 24
of Brain Dopamine 55
3.1 INTRODUCTION 55
Chapter 2
3.2 NORADRENERGIC AND ADRENERGIC
Dopamine Receptors, Signaling
NEURONS 56
Pathways, and Drugs 27
3.2.1 Historical perspectives 56
2.1 INTRODUCTION 27 3.2.2 Distribution and major functions of the brain
noradrenergic neurons 58
2.2 DOPAMINE RECEPTORS:
3.2.3 Distribution and major functions of the brain
STRUCTURE–FUNCTION
adrenergic neurons 59
RELATIONSHIP 28
2.2.1 Overview of G protein-coupled 3.3 DOPAMINERGIC NEURONS 60
receptors (GPCR) 28 3.3.1 Classification of the brain dopaminergic
2.2.2 Structural and functional classification neurons 60
of the GPCRs 29 3.3.2 Mesocortical, mesolimbic, and nigrostriatal
2.2.3 Coupling of the GPCRs to G proteins 30 dopaminergic pathways 61
2.2.4 General characteristics and regulation 3.3.3 Retinal, olfactory, and pineal dopaminergic
of the DARs 33 neurons 63
vi CONTENTS
3.4 THE HYPOTHALAMUS: STRUCTURE 4.4.5 Gastrointestinal hormones involved in the
AND FUNCTIONS 65 regulation of food intake 104
3.4.1 Anatomy of the hypothalamus 65 4.4.6 Involvement of dopamine in the control
of feeding behavior 105
3.4.2 The hypothalamic nuclei: Locations
and major neuroendocrine functions 66
4.5 NEUROENDOCRINE REGULATION
3.4.3 Catecholaminergic innervation of the OF REPRODUCTION AND SEXUAL/
hypothalamus 70
MATERNAL BEHAVIOR 107
3.5 THE HYPOTHALAMO-PITUITARY 4.5.1 Synthesis of GnRH, origin and migration
COMPLEX: NEURAL AND VASCULAR of GnRH neurons, and genetic dysfunctions 108
CONNECTIONS 71 4.5.2 Kisspeptins, GnRH pulsatility, and the role
of dopamine 108
3.5.1 Functional anatomy of the
hypothalamo-pituitary complex 71 4.5.3 Reproductive functions of PRL and reciprocal
interactions with dopamine 110
3.5.2 Embryonic development and gross anatomy
of the pituitary gland 72 4.5.4 Hyperprolactinemia and the suppression
of GnRH release 112
3.5.3 The hypothalamo-pituitary complex: Neural
connections and DA concentrations 73 4.5.5 Regulation of sexual and maternal behavior 112
3.5.4 The hypothalamo-pituitary complex:
4.6 SYNOPSIS 115
Vascular connections and DA levels
in portal blood 75 REFERENCES 115
3.6 SYNOPSIS 78
REFERENCES 78 Chapter 5
Regulation of the Pituitary Gland
by Dopamine 119
Chapter 4
5.1 INTRODUCTION 119
Endocrine Functions of Brain
5.2 NEURAL LOBE HORMONES:
Dopamine 81
VASOPRESSIN AND OXYTOCIN 119
4.1 INTRODUCTION 81
5.2.1 Ontogeny and composition of the posterior
pituitary (neurointermediate lobe) 119
4.2 CIRCADIAN RHYTHMS 82
5.2.2 Synthesis, transport, and processing
4.2.1 Circadian rhythms and their impact on health
of the neurohypophysial hormones 121
and disease 82
5.2.3 Vasopressin: Receptors, functions,
4.2.2 The neurocircuitry that controls circadian
and regulation 123
rhythms and the role of dopamine 84
5.2.4 Oxytocin: Receptors, physiology, and regulation 124
4.2.3 Dopamine and retinal rhythmicity 84
5.2.5 Effects of dopamine on the neurohypophysial
4.2.4 Dopamine and the suprachiasmatic nucleus 85
hormones 126
4.2.5 Effects of DA on the pineal: Regulation of
melatonin synthesis and release 86 5.3 INTERMEDIATE LOBE HORMONES:
4.2.6 Effects of dopamine on the circadian rhythms β- ENDORPHIN AND α-MSH 127
of circulating hormones 88
5.3.1 Structure, innervation and regulation
of the intermediate lobe 127
4.3 THE NEUROENDOCRINE STRESS
5.3.2 Synthesis and processing of POMC and its
RESPONSE 90
derivatives 128
4.3.1 Time-related, multi-facetted activation
5.3.3 Regulation of intermediate lobe hormones
of the stress response 90
by dopamine 128
4.3.2 Central dopamine and the stress response:
Interactions with the HPA axis 92 5.4 COMPOSITION AND ONTOGENY
4.3.3 Circulating dopamine and the stress response 94 OF THE ANTERIOR PITUITARY 129
4.3.4 Dopamine and the stress response: Interactions 5.4.1 Anterior pituitary structure, cell types,
with sexually dimorphic hormones 95 and dopamine receptors 129
5.4.2 Ontogeny of anterior pituitary cell lineage 131
4.4 FOOD INTAKE AND METABOLIC
HOMEOSTASIS 98 5.5 SOMATOLACTOGENIC HORMONES:
4.4.1 Control of body weight and the consequences PRL AND GH 133
of dysregulation of food intake 98
5.5.1 Structure and properties of somatotrophs
4.4.2 The hypothalamus: A major relay station and lactotrophs 134
that controls feeding behavior 98
5.5.2 PRL: Structure, synthesis, regulation,
4.4.3 Leptin, a major suppressor of appetite 101 and functions 134
4.4.4 Pancreatic hormones: Insulin and amylin 102 5.5.3 GH: Structure, synthesis, and regulation 138
CONTENTS vii
5.6 REPRODUCTIVE HORMONES: 6.6 DOPAMINE RECEPTORS IN
LH AND FSH 141 HEMATOPOIETIC AND IMMUNE
5.6.1 The gonadotrophs: Structure, properties, SYSTEMS 172
and secretory products 142 6.6.1 Dopamine receptors in lymphoid organs 172
5.6.2 GnRH and the GnRH receptor 143 6.6.2 Dopamine receptors in peripheral blood
5.6.3 FSH: Structure, synthesis, regulation lymphocytes 173
and functions 144
6.7 DOPAMINE RECEPTORS IN SKIN
5.6.4 LH: Structure, synthesis, regulation,
AND BONES 174
and functions 145
6.7.1 Skin structure 174
5.6.5 Regulation of the hypothalamo-pituitary-
gonadal axis by dopamine 146 6.7.2 Dopamine receptors in different skin
components 174
5.7 STRESS AND METABOLIC 6.7.3 Bone structure 175
HORMONES: ACTH AND TSH 147
6.7.4 Dopamine receptors in bone cells 175
5.7.1 Corticotrophs and ACTH 148
5.7.2 Major disorders associated with dysfunctions 6.8 DOPAMINE RECEPTORS IN MALE AND
of the HPA axis 149 FEMALE REPRODUCTIVE SYSTEMS 176
5.7.3 Involvement of dopamine in the regulation 6.8.1 Overall features of the reproductive system 176
of the HPA axis 151 6.8.2 The male lower reproductive system 176
5.7.4 Thyrotrophs and TSH 151 6.8.3 The female reproductive system 177
5.7.5 Disorders of the hypothalamo-pituitary-
6.9 SYNOPSIS 178
thyroid axis 153
5.7.6 Involvement of dopamine in the regulation REFERENCES 179
of the HPT axis 154
5.8 SYNOPSIS 154
Chapter 7
REFERENCES 154 Renal, Cardiovascular, and
Pulmonary Functions of Dopamine 183
7.1 INTRODUCTION 183
Chapter 6
Attributes of Peripheral Dopamine 7.2 RENAL FLUID HEMODYNAMICS
and Dopamine Receptors 159 AND HYPERTENSION 183
7.2.1 Kidney development and gross anatomy 183
6.1 INTRODUCTION 159
7.2.2 The nephron: Structure–function relationship 185
6.2 SOURCES OF CIRCULATING 7.2.3 Urine formation and composition 186
DOPAMINE 159 7.2.4 Endocrine regulation of blood pressure
6.2.1 Biosynthesis, storage, release, and by the kidney 187
metabolism of peripheral catecholamines 159 7.2.5 Dopamine: Roles in essential hypertension
6.2.2 The origin of circulating dopamine 160 and renal hemodynamics 189
6.2.3 Special characteristics of peripheral
7.3 RENAL NATRIURESIS,
dopamine 162
OXIDATIVE STRESS, AND DIABETIC
6.3 UNIQUE CHARACTERISTICS NEPHROPATHY 192
OF DOPAMINE SULFATE 163 7.3.1 Central role of the kidney in keeping
6.3.1 Sulfoconjugation of peripheral dopamine 163 electrolyte balance and osmolarity 192
6.3.2 Functions of DA-S and the role of 7.3.2 Endocrine regulation of natriuresis by the
arylsulfatase A 164 kidney 193
7.3.3 Involvement of dopamine with natriuresis 194
6.4 DOPAMINE RECEPTORS IN THE
7.3.4 Renal dopamine and oxidative stress 195
CARDIOVASCULAR, PULMONARY,
7.3.5 Dopamine and diabetic nephropathy 195
AND RENAL SYSTEMS 166
6.4.1 The cardiovascular and renal systems 166 7.4 CARDIAC FUNCTIONS 197
6.4.2 The respiratory system 167 7.4.1 Homeostasis of dopamine in the myocardium 197
7.4.2 Actions of DA on the heart under
6.5 DOPAMINE RECEPTORS
pathophysiological conditions 198
IN THE DIGESTIVE SYSTEM
AND IN ORGANS THAT REGULATE 7.5 BLOOD PRESSURE REGULATION
METABOLISM 169 IN VARIOUS VASCULAR BEDS 199
6.5.1 The digestive system 169 7.5.1 Effects of DA on various circulation systems 199
6.5.2 Metabolic regulation 171 7.5.2 Dopamine and angiogenesis 201
viii CONTENTS
7.6 RESPIRATION AND Chapter 9
OXYGEN-SENSING 202 Dopamine in the Immune and
7.6.1 Dopamine homeostasis in the upper
Hematopoietic Systems 241
respiratory tract 203
7.6.2 Dopamine involvement in upper airway 9.1 INTRODUCTION 241
pathophysiology 204
9.2 CELLS DERIVED FROM THE
7.6.3 Dopamine and carotid body functions 204
LYMPHOID LINEAGE 241
7.7 PULMONARY VENTILATION 9.2.1 T cells, B cells, and NK cells 243
AND PATHOPHYSIOLOGY 205 9.2.2 The dopaminergic system in lymphocytes
and NK cells 244
7.7.1 De novo dopamine synthesis in the lung 206
7.7.2 Actions of dopamine in the lung 206 9.3 CELLS DERIVED FROM
THE MYELOID LINEAGE 246
7.8 SYNOPSIS 208
9.3.1 The dopaminergic system in erythrocytes
REFERENCES 209 and platelets 246
9.3.2 The dopaminergic system in various
leucocyte subtypes 248
Chapter 8
9.4 AUTOIMMUNE DISEASES AND
Digestive and Metabolic Actions
NEUROPSYCHIATRIC DISORDERS 250
of Dopamine 213
9.4.1 Dopamine and autoimmune diseases 251
8.1 INTRODUCTION 213 9.4.2 Dopamine, immune system, and
neurological disorders 254
8.2 GASTROINTESTINAL SYSTEM:
9.4.3 Dopamine, immune system, and
MOTILITY 214
psychiatric disorders 257
8.2.1 Pharynx and esophagus 214
8.2.2 Stomach and duodenum 216 9.5 ENDOTHELIAL CELLS,
8.2.3 Small and large intestine 218 ANGIOGENESIS, AND COAGULATION 258
9.5.1 Endothelial cells and dopamine 258
8.3 GASTROINTESTINAL SYSTEM:
9.5.2 Angiogenesis and dopamine 259
DIGESTIVE FUNCTIONS 219
9.5.3 Blood clotting and the coagulation cascade 262
8.3.1 Salivary glands 220
8.3.2 The stomach 221 9.6 INFLAMMATION AND ALLERGIC
8.3.3 Accessory digestive organs: Exocrine REACTIONS 264
pancreas and gall bladder 222 9.6.1 Inflammation and dopamine 264
8.3.4 Small and large intestines 223
9.7 SYNOPSIS 266
8.3.5 Enteric dopaminergic system and the
gut microbiome 224 REFERENCES 267
8.4 ORGANS THAT REGULATE
METABOLISM: PANCREAS,
Chapter 10
ADIPOSE TISSUE, AND LIVER 226
Regulation of Reproduction
8.4.1 Endocrine pancreas and glucose
metabolism 227 by Dopamine 271
8.4.2 Adipose tissue 228
10.1 INTRODUCTION 271
8.4.3 The liver 231
10.2 SEX DETERMINATION AND SEXUAL
8.5 DIABETES, OBESITY, AND DIFFERENTIATION OF THE BRAIN 271
ADVERSE EFFECTS OF 10.2.1 Genetic and hormonal components of
ANTIPSYCHOTIC DRUGS 233 sexual determination and differentiation 271
8.5.1 Dopamine, diabetes, and obesity 233 10.2.2 Temporal and spatial developmental stages
8.5.2 Adverse effects of antipsychotic of sexual differentiation in the brain 274
medication on body weight and 10.2.3 Interference of the sexual differentiation
metabolic syndrome 234 program by endocrine disruptors 275
10.2.4 Association of dopamine with sexual
8.6 SYNOPSIS 235
differentiation in the brain 277
REFERENCES 236 10.2.5 Gender identity and sexual preference 278
CONTENTS ix
10.3 HYPOTHALAMO–PITUITARY Chapter 11
REGULATION OF REPRODUCTION Actions of Dopamine on the Skin
IN BOTH SEXES 279
and the Skeleton 317
10.3.1 Common features of the central control
of reproduction 279 11.1 INTRODUCTION 317
10.3.2 Involvement of dopamine in hypothalamic
11.2 SKIN STRUCTURE AND WOUND
control of reproduction and sex behavior 280
HEALING 318
10.3.3 Involvement of dopamine in the control
11.2.1 Overview of skin structure 318
of reproduction by the pituitary 281
11.2.2 The complexity of wound healing 320
10.3.4 Dopamine indirectly regulates reproductive
functions through the control of prolactin 281 11.2.3 Role of dopamine in wound healing 321
11.2.4 Polydopamine nanopolymers
10.4 MALE REPRODUCTION: TESTES used for drug delivery in
AND THE GENITAL TRACT 283 wound healing 323
10.4.1 The male gonads: Spermatogenesis 284
11.3 PIGMENTATION AND
10.4.2 The male gonads: Steroidogenesis and
MELANOGENESIS 325
protein hormone production 285
11.3.1 Overview of skin pigmentation and
10.4.3 Involvement of dopamine with testicular
melanogenesis 325
functions 286
11.3.2 Selected disorders of pigmentation 328
10.4.4 The male genital tract 287
11.3.3 Role of dopamine in skin pigmentation
10.5 FEMALE REPRODUCTION: OVARIES and its disorders 329
AND GENITAL TRACT 288
11.4 SWEATING 330
10.5.1 Unique characteristics of female
11.4.1 Overview of sweating, apocrine, and
reproduction 288
eccrine glands 330
10.5.2 The female gonads: Oogenesis,
11.4.2 Dopamine and sweating 330
folliculogenesis, and ovulation 289
10.5.3 The female gonads: Steroidogenesis 293 11.5 HAIR GROWTH 332
10.5.4 Involvement of dopamine with ovarian 11.5.1 Overview of hair growth and its hormonal
functions 293 regulation 332
10.5.5 The female genital tract 294 11.5.2 Role of dopamine in hair growth 333
10.6 FERTILIZATION, PREGNANCY, 11.6 THE SKELETON AND BONE
AND FETAL DEVELOPMENT 298 REMODELING 334
10.6.1 Overview of conception, pregnancy, 11.6.1 Overview of the skeleton and bone
and embryonic development 298 remodeling 334
10.6.2 Fertilization 299 11.6.2 Involvement of dopamine in bone
10.6.3 Blastocyst transport and implantation 301 homeostasis 336
10.6.4 Endocrine functions of the placenta 302 11.7 JOINTS, BONES, AND MUSCLES 337
10.6.5 L-Dopa and dopamine levels in different 11.7.1 Overview of joints and muscles 337
compartments of pregnancy 303
11.7.2 Involvement of dopamine in muscle
10.6.6 Development of the fetal reproductive disorders 338
organs 305
11.7.3 Involvement of dopamine in bone
and synovial joint disorders 340
10.7 PARTURITION AND LACTATION 306
10.7.1 The process of parturition 306 11.8 SYNOPSIS 342
10.7.2 Hormonal regulation of lactation 307
REFERENCES 342
10.8 NEONATAL DEVELOPMENT,
PUBERTY, AND AGING 308
10.8.1 The reproductive axis during the neonatal Chapter 12
and prepubertal periods 308 Dopamine and Tumorigenesis in
10.8.2 Hormonal control of puberty and disorders Reproductive Tissues 345
of puberty 309
12.1 INTRODUCTION 345
10.8.3 Aging of the reproductive system 310
12.2 PITUITARY TUMORS 346
10.9 SYNOPSIS 311
12.2.1 Prevalence, classification, and molecular
REFERENCES 311 characterization of pituitary tumors 346