Endocrinology, lecture on Adrenal Medullary Catecholamines
XVI. Chromaffin Tissue - Adrenal Medulla
A. Chromaffin tissue in mammals is found in the center (medulla) of the
adrenal gland
1. in other classes chromaffin tissue is associated with "cortical"
tissue but is not necessarily medullary
a. juxtaposition is related to function and is derived
evolutionarily many times
B. Chromaffin tissue is highly innervated by the sympathetic nervous system
1. may be thought of as postsynaptic neuron
a. which terminates on capillary bed
i. derived from neural crest tissue similar to those of
the sympathetic ganglia
(1) nerve growth factor (NGF)
plays an important role in development
2. stimulated by the neurotransmitter ACh
a. all presynaptic neurons of the sympathetic and
parasympathetic ns secrete ACh
b. postsynaptic neurons of the sympathetic ns secrete NE
3. Chromaffin tissue secretes NE (1/3),
but mostly Epi (in humans/rats)
a. catecholamines
XVII. Catecholamines
A. DA, NE, and Epi
1. each is secreted as an end product
a. all are hormones
i. DA and NE most often act as neurotransmitters
ii. Epi is also a central neurotransmitter
B. Biosynthesis
1. aa Tyrosine is converted by tyrosine hydroxylase
a. limiting step
i. stimulated by ACTH
ii. activated by phosphorylation via cAMP/Protein Kinase A
(1) negative feedback by DA, NE, Epi
2. into DOPA (L-DOPA is the only natural form)
a. DOPA decarboxylase = aaa decarboxylase
(aaa= aromatic amino acid)
3. DA = dopamine
a. DBH = dopamine b-hydroxylase
i. stimulated by ACTH
4. NE
a. PNMT = phenylethanolamine N-methyltransferase
i. stimulated by glucocorticoids
(1) delivered by a local portal system
b. TH, DBH, & PNMT are similar proteins with common
gene coding sequences
5. Epi
C. Catabolism
1. very rapid, each catecholamine into different metabolites
2. 2 main enzymes
a. cathechol O-methyltransferase = COMT
i. Epi ® metanephrine or NE ® normetanephrine
b. monoamine oxidase = MAO
i. very common
ii. deaminates
D. Receptors and Uptake
1. Adrenergic Receptors
a. a
i. a1 binds Epi > NE
(1) activates IP3 /DG /PKC /Ca++
(2) smooth muscle contraction: arteries in skin, kidney
and digestive system, sphincters, iris (pupil dilates)
ii. a2 binds Epi > NE
(1) may be presynaptic or postsynaptic
(a) presynaptic for local negative feedback
(2) activates Gi ® inhibits AC/cAMP
(3) may oppose actions of b-receptors: ¯ insulin
secretion & lypolysis
b. b
i. b1 & b2 bind Epi > NE
(1) activate Gs /AC /cAMP /PKA
ii. b1 mostly cardiac
(1) ñ HR, contractility, conduction
velocity, and coronary artery dilation
(2) ñ lypolysis
iii. b2 ñ glycogenolysis and gluconeogenesis
and insulin secretion
(1) dilate blood vessels in skeletal muscle but relax
smooth muscles in the digestive tract, uterus, and lungs
(2) stimulate renin secretion
2. Dopaminergic receptors are grouped into 2 main subfamilies D1 and D2
a. DA1: DA1 & DA5
DA2: DA2, DA3, DA4
b. 2nd messengers:
i. D1 subfamily = Gs / cAMP
ii. D2 family = Gi
3. Uptake, Re-uptake
a. catecholamines are taken up by cells
in which they are stored or degraded
b. neural cells which make DA or NE re-incorporate neurotransmitter
secreted, and reuse it
i. active transport
c. non-neural cells actively take up catecholamines
and then degrade them with COMT