Mineralocorticoids:

Mineralocorticoids:
1
Apparato juxtaglomerulare:
2
3
4
Ca2+
5
6
low
pressure
beta-adrenergic receptor
PGE2 receptor
ΔV
adenosine
angiotensin II
7
Na+
Na+
Na+
8
Sistema reninaangiotensinaaldosterone:
(lung)
ANP
9
ER
10
11
 volume of zona
glomerulosa
 cardiac
contractility
vasoconstriction, decreased
glomerular filtration
baroreceptors in the carotid
sinuses and aortic arches
beta receptors
12
(captopril, enalapril)
(liver)
13
kidney (P cells: distal tubule, collecting duct)
similar effects on
colon, sweat and
salivary glans
~
 ATP synthesis
sodium
reabsorption
exceeds
potassium
excretion
14
feed-back mechanism:
 ANP
 renin
decreased pressure afferent arteriole
sympathetic reflexes
low NaCl in macula densa
 angiotensin II
 aldosterone
 Na+ uptake
only 2% of total sodium filtered is reabsorbed,
but it corresponds to 3.5 l of fluid!
 blood volume
 renin
15
free cortisol in blood is about 100 times higher than free aldosterone
MR binds aldosterone and cortisol with equal affinity, and GRE binds
both MR and GR, but GR has a greater affinity for cortisol than for
aldosterone
In kidney:
glycyrrhizic acid
hypertension,  K+
HSD II
high activity
very low activity
16
17
(Lys in pig)
Primary structures of oxytocin and arginine vasopressin (AVP)
18
marker of acute illness
copeptin
19
20
Liver
Glycogenolysis
CNS
Neurotransmission
(V3R)
and adhesion
21
PKA
22
AQP1
AQP1
23
24
ANP
+
ADH
25
thick ascending limb of the loop of Henle
ADH
26
27
stretch-inhibited (SI) nonselective cation channels:
28
( 10-15%)
volemia
( 1-2%)
osmolarity
29
30
31
Other stimuli:
nausea, vomiting
pregnancy
menstrual cycle
Inhibitors:
alcohol
caffeine
32
33
Half-life: 10-30 min
Catabolism: liver, kidney
Diabetes insipidus (deficit of AVP)
Nephrogenic diabetes insipidus (deficit of V2-R, AQP2 or other)
Acquired deficits of AQP2: bipolar disorder (lithium therapy)
34
35
atrial natriuretic factor (ANF, ANP): atria
brain natriuretic peptide (BNP): atria, ventricle, brain,  after heart failure
C-type natriuretic peptide (CNP): brain, lacks natriuretic activity
36
ANP, BNP
CNP
37
38
Natriuretic peptide-dependent smooth muscle relaxation
39
↓ norepinephrine
40
Urodilatin:
• secreted by the distal tubule and collecting duct
• not present in the systemic circulation (it influences only the function of
the kidneys)
• stimulated by a rise in blood pressure and an increase in blood volume
• it inhibits NaCl and water reabsorption across the medullary portion of
the collecting duct
• it is a more potent natriuretic and diuretic hormone than ANP
41
42
Adrenal medulla:
chromaffin cells
43
44
45
Epinephrine is about five times as abundant in the human adrenal
medulla as norepinephrine.
Only norepinephrine is found in postganglionic sympathetic neurons
and extra-adrenal chromaffin tissue.
46
CO2
47
48
49
DBH, dopamine betahydroxylase
PNMT,
phenylethanolamine-Nmethyltransferase
(Cu, ascorbate)
(SAM)
50
vesicular monoamine transporter (VMAT):
51
•
•
•
•
•
pain
hemorrhage
physical exercise
hypoglycemia
hypoxia
brain
52
kinases
+
catecholamines
glucocorticoids
+
Na+ entry
depolarization
increase of Ca++
53
54
half-lives of medullary
hormones in the peripheral
circulation = 10-15 sec
Norepinephrine
Epinephrine
ATP
Enkephalins
β-endorphin
Chromogranin A and B
Dopamine-β-hydroxylase
55
56
(noradrenaline
re-uptake
inhibitors)
cocaine,
tricyclic
antidepressants
NET
57
58
DOPGAL = 3,4-dihydroxyphenylglycolaldehyde
SAM
SAH
59
Monoamine oxidase
60
MAO, Monoamine oxidase
COMT, catechol-O-methyltransferase
AD, alcohol dehydrogenase
AO, aldehyde oxidase
conjugation (sulfate, glucuronate)
 VMA = pheochromocytoma
urine
61
Effetti metabolici dell’adrenalina:
•  glicogenolisi e  glicogenosintesi (muscolo, fegato)
•  gluconeogenesi (fegato)
•  glicolisi (muscolo)
•  lipolisi (tessuto adiposo)
•  glucoso e acidi grassi nel sangue
•  glucagone
•  insulina
62
Effetti fisiologici di adrenalina e noradrenalina:
• vasocostrizione cutanea, intestinale e renale
• vasodilatazione muscolare,  trasporto O2 al muscolo
• aumento della pressione sistolica
• stimolazione della gittata e della frequenza cardiaca
• rilassamento intestinale
• broncodilatazione
• ritenzione renale di Na,  renina
• aggregazione piastrinica
• midriasi
• sudorazione
• brividi, erezione dei peli
• contrazione milza  linfocitosi
• ansia, veglia, tremori, attivazione psicomotoria, maggiore
intensità emotiva
63
64
Dopamine affects cognition and learning in the basal ganglia,
as well as pleasure and behavior in the limbic system.
65
In the pituitary dopamine inhibits the release of prolactin.
Dopamine is used in patients with shock or heart failure to
increase cardiac output and blood pressure.
66
morbo di Parkinson: degenerazione di neuroni dopaminergici
67
DAT:
dopamine
transporter
DAT
Morbo di Parkinson:
tremori
rigidità
lentezza nei movimenti
problemi cognitivi e comportamentali
corpus striatum
68
69
schizofrenia: iperattività di neuroni dopaminergici
mescalina:
strutturalmente simile
alla dopamina, induce
uno stato similschizofrenico
70
melanocortinergic system
agonists: α-, β-, and γ-MSH
antagonists: agouti-related protein (AGRP, hypothalamus) and
agouti protein (AG, skin)
Receptors:
MC1-R: MSH and ACTH receptor, skin
MC2-R: ACTH receptor adrenal gland, skin and adipocytes
MC3-R/MC4-R: turning off food intake in brain (KO mice: obese)
MC5-R: ACTH receptor in many tissues
71
• Cart = cocaine- and
amphetamine-regulated
transcript
• α-MSH, α-melanocyte
stimulating hormone
• Npy, neuropeptide Y
• Pomc, proopiomelanocortin
72
73
74
75
with
76

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