Catecholamines and the Sympathoadrenal System Flashcards
What is epinephrine?
It is a major hormone release by the adrenal medulla.
What causes the release of epinephrine?
Stress induces the release of it into the blood stream, this hormone prepares the organism for “fight or flight”.
How are catecholamines activated?
They are activated by the sympathetic nervous system; the adrenal medulla is a modified sympathetic ganglion with post ganglionic cells but no axons.
What makes NE and what does it do?
It is made by cell bodies in the locus coeruleus in the brain stem. In the periphery it is the postganglionic transmitter of the sympathetic nervous system.
What are the responses to epinephrine?
Arousal: alerting, pupillary dilation, piloerection, sweating, bronchial dilation, tachycardia, inhibition of smooth muscle in the GI tract and others.
Metabolic: acts to increase ready rule via stimulation of glycogenolysis in the liver and muscle and stimulates lipolysis in fat cells by activating lipase
As a result metabolic rate increases by ~20-30%
What do beta receptors do?
They stimulate hepatic glycogenolysis. in the muscle they stimulate glycogenolysis and the production of lactic acid which is used for gluconeogenesis in the liver. They are also able to stimulate pancreatic A cells.
What do alpha receptors do?
Through them catecholamines inhibit pancreatic B cells.
What is the hormonal control of adipocyte lipolysis?
- Agonists are bound to beta-adrenergic receptors (b-AR), coupled to adenylate cyclase (AC) via the stimulatory G protein, this increases the levels of cAMP.
- This will activate PKA which phosphorylates hormone sensitive lipase (HSL) t three serine residues and also perilipin A on multiple sites.
- PKA phosphorylation of HSL causes translocation from the cytosol to the lipid droplet, whereas phosphorylation of perilipin by PKA alleviates the barrier function of this protein and prompts its active participation in the lipolytic process.
- In hormonally quiescent adipocytes, HSL appears to be phosphorylated at a fourth serine residue, presumable by the 5’-AMP-activated protein kinase (5’-AMPK).
What are the physiological responses to adrenal epinephrine/norepinephrine?
- Increased rate and force of contraction of the heart muscle via beta receptors.
- Constriction of blood vessels: norepinephrine, in particular, causes widespread vasoconstriction, resulting in increased resistance and hence arterial blood pressure.
- Dilation of bronchioles: assists in pulmonary ventilation. Via beta receptors.
- Stimulation of lipolysis in fat cells: this provides fatty acids for energy production in many tissues and aids in conservation of dwindling reserve of blood glucose.
- Increased metabolic rate: oxygen consumption and heat production increase throughout the body in response to epinephrine. Medullary hormones also promote breakdown of glycogen in skeletal muscle to provide glucose for energy production.
- Dilation of the pupils
- Inhibition of certain “non-essential” processes: an example is inhibition of gastrointestinal secretion and motor activity.
What are common stimuli for the secretion of catecholamines?
- Exercise
- Hypoglycemia
- Hemorrhage
- Emotional distress
How are catecholamines synthesized?
First it is converted from dopamine via the enzyme dopamine-B-hydroxylase.
NE is loaded into vesicles via VMAT.
NE is then cleared from the synapse by the norepinephrine transporter (NET)
- NET is the target for amphetamine.
- NE is degraded by MAO and catechol-O-methyltransferase (COMT)
How do catecholamine receptors work?
- E and NE acts on alpha- and beta-adrenergic receptors.
- Both are G-protein coupled receptors.
- Activation of alpha-1 receptors results in slow depolarization due to closing a K+ channel.
- Activating alpha-2 hyperpolarizes the postsynaptic cell by opening a K+ channel.
What happens when alpha receptors are activated?
- Vasoconstriction of arteries to the heart (coronary artery)
- Vasoconstriction of veins
- Decrease motility of smooth muscle in gastrointestinal tract.
What are beta adrenergic receptors?
They are the target of “beta-blockers” like propanolol.
What are the specific actions of the B1 receptor?
- increase cardiac output by increasing heart rate.
- Increased cardiac stroke volume (by enhancing contractility)
