Flashcards in Adrenergic Physiology Deck (31):
What does the sympathetic nervous system regulate homeostatically?
HR, force of cardiac contraction, vasomotor tone, blood pressure, bronchial airway tone, and carbohydrate and fatty acid metabolism.
What are the endogenous neurotransmitters?
catecholamines: dopamine, epinephrine, and norepinephrine
What is similar in molecular structure between the catecholamines?
The catechol 6 carbon ring (OH on carbon 3 and 4), 2 carbon chain with an amine (NH2).
How does dopamine differ?
It has 2 Hs on the beta carbon (first carbon next to catechol ring).
How does norepinephrine differ?
It has an H and OH on the beta carbon (first carbon next to catechol ring).
How does epinephrine differ from norepinephrine?
One of the amine hydrogens is changed to a methyl group: NHCH3
How are dopamine and norepinephrine synthesized?
(She said she won't ask enzymes).
Within an adrenergic nerve.
1. Tyrosine is transported into the nerve terminal with Na+ where it is hydroxylated via tyrosine hydroxylase to form Dopa.
2. Dopa is decarboxylated to dopamine, which is transported into the vesicle via VMAT (vesicle monamine transporter).
3. Inside the vesicle dopamine is hydroxylated to norepinephrine via DA-beta-hydroxylase (not loose in the cell but within the membrane) with ascorbic acid (vit. c).
4. Vesicles are released via depolarization and Ca2+ influx.
How is epinephrine synthesized?
from the norepinephrine in the adrenal glands (chromaffin cells) using phenylethanolamine N-methyltransferase. Makes sense because remember epinephrine has an added methyl group on the amine.
It is then secreted into the BLOOD.
What are the 3 methods of neurotransmitter termination?
What are the 2 enzymes for neurotransmitter termination via metabolism?
1. monamine oxidase (MAO) 80%
2. catechol O-methyltransferase (COMT) 20%
Where is monamine oxidase (MAO) found and what does it do?
In the mitochondria of the nerve terminals and it oxidatively deaminates the alpha carbon on the catecholamines.
*Think M= mitochondria, and A= alpha carbon
Where is catechol O-methyltransferase (COMT) found and what does it do?
found in the Cytoplasm of liver cells and some in the adrenergic nerve synapse. It transfers a methyl group to the 3 position Oxygen of the CATECHOL end.
*Think C= cytoplasm, and O= oxygen
How does the reuptake system of neurotransmitter termination work?
uses active transport to take up various amines from the synapse, moving it to the cytoplasm where they are deaminated by MAO and repackaged into vesicles.
How does the dilution system of neurotransmitter termination work?
The neurotransmitters diffuse out of the synapse or can be taken up at extraneuronal sites (ex. glia).
What is the most important way norepinephrine is terminated?
Via reuptake pumps. 80% reaccumulates into vesicles and 20% is either metabolized by MAO, diffuses away, or is metabolized by COMT (uptake via post-synaptic cell).
What do alpha 1 receptors do to blood vessels?
cause vascoCONSTRICTION, increasing total peripheral resistance (TPR) and thus increasing blood pressure. These are found in all blood vessels and found post-synaptically.
What do alpha 1 receptors do to mucosa?
decongestion to allow for increased airflow for O2 delivery to lung capillaries.
What do alpha 1 receptors do to the eye?
cause mydriasis (pupillary dilation) via radial muscle of iris to increase visual field by allowing more light to enter.
What do alpha 1 receptors do to the skin?
cause pilomotor erection (makes your hair stand up).
What do alpha 1 receptors do to blood glucose levels?
cause hyperglycemia to increase glucose for more glycolysis and TCA cycle production of ATP.
Is the alpha 2 receptor a pre-synaptic or post-synaptic receptor?
pre-synaptic, and when activated will reduce the release of norepinephrine in the PNS, and reduce sympathetic outflow in the CNS. Aka it slows the sympathetics down.
Where are beta 1 receptors found?
mostly in the HEART, to some degree also kidneys (juxtaglomerular cells) and fat tissue.
What do beta 1 receptors do?
increase HR, force of contraction, and velocity of conduction of the heart to overcome the vasoconstriction of the vessels. Also acts to increase renin production of the juxtaglomerular apparatus in the kidneys (increasing BP).
Dopamine will cause renal dilation (increase renal blood flow) via D1 receptors at low doses, cardiac activation at medium does via B1 receptors, and alpha 1 presser effects in high amounts.
Where are beta 2 receptors found?
Smooth muscle, skeletal muscle, blood vessels, heart, bladder, liver, and GI.
What are the actions of beta 2 receptors?
- vasodilation of blood vessels in skeletal muscle, pulmonary, and coronary arteries (ADENOSINE for coronaries; carried by paramedics).
- uterus relaxation to prevent birth in scary situation
- bladder increase in sphincter tone and decrease in detrusor muscle tone
- lactic acidemia
Can prolonged stress via alpha 1 (uterine contraction) receptors override the beta 2 uterus relaxation?
YES, leading to labor (remember prolonged only).
What is the order of agonist potency for alpha 1 and 2 receptors?
epinephrine > NE > DA > ISOP
What is the order of agonist potency for beta 1 receptors?
ISOP > EPI=NE
What is the order of agonist potency for beta 2 receptors?
ISOP > EPI > NE > DA
Would you need a high or low dose of ISOP for effectiveness on beta 1 and 2 receptors?
LOW because it is the most potent for these