ADRENAL MEDULLA:
key player in response to stress
Consists of modified post-ganglionic sympathetic axons that
release predominantly
epinephrine (instead of norepinephrine)
ADRENAL MEDULLA:
key player in response to stress
Consists of modified post-ganglionic sympathetic axons that
release predominantly
epinephrine (instead of norepinephrine)
Ach NE Nicotinic R Ach Sympathetic nerves Adrenal medulla Epi Chromaffin
cell
STRESS ADRENAL
MEDULLA
EPINEPHRINE FIGHT OR FLIGHT
STRESS?
INJURY/DISEASE
EMOTION (fear/anxiety)
EXERCISE
ENVIRONMENTAL
(temperature/dehydration)
STRESS INDUCES A COORDINATED
RESPONSE of
Adrenal cortex
Adrenal medulla
Autonomic nervous system
± involuntary/voluntary behaviors
STRESS Symp.
NS Adrenal
Cortex Adrenal
medulla NE Epi Cortisol Secretion of epi stimulated by both
preganglionic input and glucococorticoids portal system
from cortex
to medulla
Hypoglycemia causes selective
release of EPI, unaccompanied by global changes in sympathetic
nerve
activity
TROPHISM
Cortisol in portal system from cortex
Levels of cortisol in medulla are 100X higher
than in systemic circulation.
Cortisol promotes formation of Epi from NE. RELEASE of EPI
Ach Depolarization Voltage-activated
Ca channels [Ca2+ ]i exocytosis EPI release regulated by ACTH/cortisol & by
preganglionic sympathetic input
80% of chromaffin cells have portal supply.
Receive cortisol; produce epinephrine 20% of chromaffin cells have no portal supply.
No cortisol; produce norepinephrine.
But NE secretion not physiologically important.
Even under high stress, plasma NE levels
are usually sub-threshold In Addison’s disease, plasma cortisol is
reduced, and plasma epi levels are reduced
from 300 to 100 pM.
But EPI secretion not physiologically
important under unstressed conditions.
i.e. Normal plasma EPI level is below
physiological threshold
HO HO CH.CH 2 .NH 2 OH NOREPINEPHRINE HO HO CH.CH 2 .NH.CH 3 OH EPINEPHRINE DOPA DOPAMINE HO CH 2 .CH.COOH NH 2 TYROSINE tyrosine hydroxylase
(rate limiting step) ACTH
ACh cortisol SYNTHESIS
The catecholamines compete with tyrosine for tyrosine hydroxylase.
Release of catecholamines relieves this
product inhibition resulting in stimulation of Epi formation NEGATIVE FEEDBACK
Plasma epi/NE levels ≈ 10–9 M
NE rarely reaches physiologically significant
levels in plasma. EPI is the important
Adrenomedullary hormone
Onset and decay of increased plasma
EPI levels both rapid; T1/2 ≈ 10 sec
(response to stress should be rapid and short-lived)
97% EPI/NE broken down to inactive forms by
MAO (monoamine oxidase)
COMT (catecholamine-O-methyl transferase)
NE a = b1 >> b2 Epi a = b1 = b2 Pharmacologically, EPI is like NE,
but has additional b2-receptor
(metabolic) effects
Sympathetic nerve stimulation (NE)
and blood EPI are synergistic. There
is a lot of overlap in what they do.
EPI’s CARDIOVASCULAR EFFECTS
HEART
HR
Contractility
Venous constriction
Cardiac output
BLOOD VESSELS
Contracts arterioles in most tissues (a).
Relaxes those in striated muscle and
heart (b).
Redistribution of blood flow to muscle
while maintaining coronary/cerebral
flow
BLOOD PRESSURE
CO + Ra Pa
WHAT ELSE?
1) medulla cortex
2) opioids
3) anti-bacterial peptides
“Antibacterial peptides are present in chromaffin
cell secretory granules” (lots of them; most
derived from chromogranin; released by nerve
stimulation)
4) adrenomedullin
(hypotensive agent, actions similar to those of ANP,
i.e. diuresis and natriuresis)
cortisol A miniature (backup)
hypothalamic/pituitary
axis within the adrenal medulla System up-regulated
in hypophysectomized
rats CRH ACTH
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