lectures - adrenal medulla: catecholamines and adrenergic receptors

what is the origin of the adrenal cortex

embryonic origin - mesoderm

what is the origin of the adrenal medulla

embryonic origin - neural ectoderm

what is PNMT

key in medullar cells to change norepi to epi

the adrenal medulla part of what NS

autonomic sympath NS

describe epi

produced exclusively by adrenal medullar cells

80% adrenal catecholamines

how big is the adrenal medulla

small, only makes up 10% of total adrenal weight

describe chromaffin cells

highly specialized neural system originating in neural crest which migrate to adrenal medulla and paraganglia during embryo/fetal development

in some species like sharks where is the adrenal medulla in comparison to cortex

completely separate from cortex

where do preganglionic cholinergic neurons end

in paraganglia

what are paraganglia

groups of neuroendocrine cells similar to adrenal medulla that are part of the sympath NS

what controls catecholamine release from sympath neurons and adrenal medulla

CNS

adrenal medullary cells near blood vessels get exposed to...

relatively high levels of cortisol as blood from cortex exits gland

does epi ↑ gluconeo

yes

cort that diffuses into adrenal medulla does what

helps to activated GPCR that enhances production of epi and norepi

what are some sources of tyrosine

beef pork chicken fish cheese nuts soybeans

how does cortisol affect PNMT

enhances its gene expression

what are catecholamines

molcs that have a catechol nucleus of 2 hydroxyl side groups + SC amine

what are some catecholamines

dopamine, norepi, and epi

how much epi is made

80-85% of catecholamines secreted by medullar cells

particularly in cells bathed by blood coming from adrenal cortex

how much norepi is made

15-20% of catecholamines secreted by medullar cells

most norepi in circulation originates from leakages of adrenergic neurons

where do catecholamines originate from

chromaffin cells and sypath neurons

epi and norepi are released by medulla upon activation of...

preganglionic sympath nerves innervating tissue

what is the primary source of circulating norepi

spillover from sympath nerves innervating blood vessels

what happens to most norepi released by sympath nerves

taken back up by nerves where it is metabolized

small amount diffuses into blood and circulates

at times of high sympath nerve activation the amount of norepi...

increases dramatically

what are some common stimuli for secretion of adrenomedullary hormones

exercise

hypoglycemia

hypotension

hypoxia

hemorrhage

heart failure

exposure to cold

pain

emotional distress

what are some actions of epi

↑ dilation of coronary arteries/muscle vessels

↑ BP

↑ peripheral vasoconstriction to get blood to imp. spots

↑ stroke volume (strength of heart contractions)

↑ heart rate

↑ breakdown of hepatic glycogen

describe the fight or flight response

extremely fast response mediated by nervous reflex, epi released from adrenal medulla, and norepi release in adrenergic synapses

what does epi do in adipose tissue in response to hypoglycemia

↑ lipolysis

↑ gluconeo

what does epi do in liver in response to hypoglycemia

↑ glycogen breakdown

↑ gluconeo

what are some effects of epi and norepi in stress response

↑ heat/respiratory rates

↑ perspiration

↑ blood to muscles

↑ muscle strength

↑ cognitive activity

- GI activity

norepi primarily functions as...

NT for cardiac effects

both norepi and epi influence...

vascular tone

epi affects what kind of processes

metabolic processes like carbo metabolism

what kind of receptors do catecholamines use

cell mem receptors called α and ß adrenergic receptors

what adrenergic receptor has the highest affinity for epi

ß2

at low plasma concentrations epi predominately stimulates what

ß2 adrenergic receptors causing vasodilation

at higher plasma concentrations epi stimulates what

α1 adrenergic receptors that override vasodilation and cause vasoconstriction

describe α1 adrenergic receptor

norepi>epi

Gq

PLC

↑ IP3, DAG, Ca

describe α2 adrenergic receptor

norepi>epi

Gi

inhibits AC

↓ cAMP

describe ß1 adrenergic receptor

norepi=epi

Gs

AC

↑ cAMP

describe ß2 adrenergic receptor

epi>>>norepi

Gs

AC

↑ cAMP

describe ß3 adrenergic receptor

norepi>epi

Gs

AC

↑ cAMP

is each adrenergic receptor subtype encoded by a diff gene

yes

what does the α2 work through

Gi which is inhibitory of AC cycle

where can α1 be found

vascular smooth muscle - ↑ vasoconstriction

liver - ↑ glycogen breakdown + gluconeo

where can α2 be found

preganglionic nerves - ↓ release of NT

where can ß1 be found

myocardium - ↑ force and rate of contriction

kidney - ↑ secretion of renin

where can ß2 be found

vascular smooth muscle - ↓ vasoconstriction

bronchiolar smooth muscle - ↓ contraction (bronchial dilation)

liver - ↑ glycogen breakdown + gluconeo

what are the ß1 mediated epi response

increased HR and contraction force/stroke volume

what are the α1 mediated epi response

vasoconstriction in most systemic arteries and veins

vasoconstriction in muscle and liver at high concentrations

what are the ß2 mediated epi response

vasodilation in muscle and liver vasculatures at low concentrations

what are the most important adrenergic receptors

α1 and ß2 receptors

what is the overall cardiovascular response to low-to-moderate circulating concentrations of epi

↑ cardiac output and redistribution of cardiac output to muscular and hepatic circulations with small change in arterial pressure

why does arterial pressure not change much in response to low-to-moderate circulating concentrations of epi

system vascular resistance falls due to ß2 adrenoreceptor activation

why does epi increase arterial pressure at high plasma concentrations

due to binding to α1 adrenoreceptors on BVs which offset ß2 mediated vasodilation