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Prof.Dr.Arzu SEVEN
Sympathoadrenal system
Parasympathetic
nervous system
with
cholinergic pre
and
postganglionic
nerves
Sympathetic
nervous system
with cholinergic
preganglionic and
adrenergic
postganglionic
nerves
+
adrenal medulla
 Adrenal medulla is actually an extension of the
sympathetic nervous system where choromaffin cells
produce catecholamine hormones:
 Dopamine
 Norepinephrine
 Epinephrine(80%)
 Adrenal medulla is a specialized ganglion without
axonal extension
 Its chromaffin cells synthesize , store and release
hormonesendocrine organ
 Catecholamines are major elements in response to
severe stress
 Stress hormones:
 Catecholamines
 Glucocorticoids
 Growth hormone
 Vasopressin
 Angiotensin II
 Glucagon
 Conversion of tyrosine to epinephrine requires 4
sequential steps;
1. Ring hydroxylation
2. Decarboxylation
3. Side-chain hydroxylation
4. N_methylation
 Tyrosine hydroxylase is the rate limiting enzyme
 It functions as an oxidoreductase , with
tetrahydropteridine as a cofactor
 Feedback inhibition by catecholamines
 Competitively inhibited by tyrosine derivatives α_methyltyrosine and by α,α,dipyridyl
 Catecholamines can’t cross the blood_brain barrier
 L_Dopa, the precursor of dopamine, readily crosses
the blood brain barrier used in the treatment of
Parkinson’s disease
 Dopa decarboxylase requires pyridoxal phosphate ,
competetively inhibited by α metil dopa
 Dopamine β hydroxylase (DBH) is a mixed function
oxidase, uses ascorbate as an electron donor, copper at
the active site and fumarate as modulator,conversion
occurs in the secretion granule
 PNMT is induced by glucocorticoid hormones
,conversion occurs in the cytoplasm
 Catecolamines enter the granule via an
ATP_dependent transport mechanism and binds this
nucleotide in a 4:1 ratio(hormone:ATP)
 NE is stored in these granules, can be N_methylated
 Exocytotic release of NE and E are calcium dependent
and are stimulated by cholinergic and β_adrenergic
agents and inhibited by α_adrenergic agents
 The adrenal medulla, unlike the sympathetic nerves,
does not have a mechanism for the reuptake and
storage of discharged catecholamines
 The epinephrine discharged from the adrenal goes to
the liver and skeletal muscle
 Very little adrenal NE reaches distal tissues
 Catecholamines circulate in plasma in a loose
association with albumin
 They have an extremely short biological half life (10-30
sec.)
 Catecholamines are rapidly metabolized by
catechol_O_methyl transferase(COMT) and
monoamine oxidase (MAO) to form O_methylated
and deaminated metabolites
 The concentration of metanephrines or VMA in urine
is elevated in > 95% of patients with
PHEOCHROMOCYTOMA
 Tumor of adrenal medulla NE causes hypertension
by activating α_1_adrenoceptors on vascular smooth
muscle, and epinephrine increases heart rate by
activation β1_adrenoceptors
 Hypertension may be paroxysmal and severe, leading to
stroke or heart failure
 Catecholamines can be classified by their mechanism
at action. They act through 2 major classes of
receptors ;
 α adrenergic
 β adrenergic
α
α1
α2
β1
Β
β2
 Epinephrine binds and activates both α and β
receptors
 NE at physiologic concentrations primarily binds to α
receptors
 The catecholamine receptors are members of the G
protein-linked class of receptor
 Hormones that bind to β1, γ, β2 receptors activate
adenylyl cyclase, whereas hormones that bind to α2
receptors inhibit the enzyme
 α1 receptors are coupled to processes that alter
intracellular Ca+2 concentrations or modify
phosphatidyl inositide met. (or both)