Adrenal Medulla and Paraganglia
What catecholamine is released from the adrenal medulla in the greatest amounts? What do neurons mainly release?
1. Epinephrine 2. Norepinephrine
What pathway do alpha1- adrenergic receptors stimulate? What parts of the body are activated by E/NE binding to alpha 1 adrenergic receptors? What is the effect on tissues? How are antagonists for the alpha- adrenergic receptors used?
1. Gq pathway 2. Activation in liver, eye, skin, intestine, and smooth muscle results 3. Vasoconstriction of the arterioles and smooth muscle contraction ,Pupillary dilation, Increased peripheral resistance and systemic arterial blood pressure 4. They are used to treat enlarged prostate, hypertension, and PTSD
What is the effect of high concentrations of cortisol on PNMT expression? What is produced? What are the levels of E linked to then?
1. High concentrations of cortisol enhance the expression of the gene encoding PNMT 2. to produce epinephrine 3. epinephrine levels linked to cortisol levels
What happens to NE when PNMT is present? What happens to cytoplasmic NE in most cells of the adrenal medulla ?
1. If PNMT is present, norepinephrine will be converted into epinephrine 2. In most cells of the adrenal medulla, cytoplasmic norepinephrine is converted to epinephrine via PNMT
What do E/NE break down into in the adrenal medulla, what are the metabolites that result from E/NE breakdown used for frequently?
1. In the adrenal medulla, E and NE breakdown into metanephrine, normetanephrine, and VMA - these metabolites are frequently used as a diagnostic tests for NE and E for longer half-life
What is the adrenal medulla structurally comprised of?
Chromaffin cells...
What are the hormones that the SNS uses for signaling?
Epinephrine and Norepinephrine
Ach--> Catecholamines pathway
Food-->Phenylalanine in liver--> Produces Tyrosine--> Tyrosine Hydroxylase = rate limiting step--> DOPA--> DOPA decarboxylase--> DOPA (medulla, S.neurons, and renal tubule)--> DOPA beta-hydroxylase (in stored vesicles)--> NE (mainly in CNS and peripheral sympathetic paraganglia and nerves )-->[Cortisol]-->PNMT--> E, mainly in medulla
What is the rate-limiting step in synthesis of epinephrine & norepinephrine?
From tyrosine to DOPA via Tyrosine hydroxylase
What should you avoid before diagnostic tests for catecholamines?
Should avoid coffee, tea, bananas, chocolate, cocoa, citrus fruits, vanilla, stress, and heavy exercise several days before test
What is the precursor for epinephrine & norepinephrine?
Tyrosine is the precursor
Where is norepinephrine mainly produced and secreted?
...1.CNS 2.peripheral sympathetic paraganglia 3.nerves
Where is epinephrine mainly produced and secreted?
...E is mainly produced and secreted by the adrenal medulla
Do pheochromocytoma's often affect 1 or both adrenal medulla's ?
1
What type of receptor does Ach bind to on chromaffin cells of the adrenal medulla? What hormone is produced mainly?
1. Ach binds to nicotinic acetylcholine receptors (nAchR) on Chromaffin cells 2. E is mainly produced, NE is also produced
95% of circulating E is derived from where? What does adrenal medullary secretion account for in terms of circulating NE?
1. Adrenal Medulla 2. Adrenal medulla only secretes 7% of circulating NE
Upon release what do E and NE travel through the blood bound to? What type of receptors does E/NE bind to in target cells?
1. Albumin 2. Various adrenergic receptors - ALpha type alpha 1a,b, d
What automatic response does the SNS help to coordinate? How does it do this?
1. Automatic fight or flight 2. SNS-->Adrenal Medulla-->Secretes epinephrine and norepinephrine -->Directly stims. cardiac output and blood flow to muscles while diverting blood flow away from visceral organs
What are the half-lifes of catecholamines , and is checking the blood and urine for them comprehensive?
1. Catecholamines are quickly removed from the bloodstream and have a circulating half-life of less than 2 minutes - we can still check for these in the blood and/or urine, but not comprehensive
What type of cells does the adrenal medulla contain? what are the special characteristics of these cells? What are they an extension of ?
1. Chromaffin cells= paraganglia 2. They are neuroendocrine cells that are adjacent to sympathetic neurons 3. The NS= neurons without axons
What is common to develop in the adrenal gland from immature neuroblasts? What type of patient is commonly seen with this tumor? what can it secrete high amounts of?
1. Neuroblastomas 2. Children under 5 3. Catecholamines
What do nonselective Beta-blockers block? What do they help reduce, increase?
1. Nonselective β-blockers block all β- adrenergic receptors 2. can reduce hypertension, increase bronchoconstriction, and increase peripheral vasoconstriction
What releases NE predominantly? What releases E. predominantly?
1. Norepinephrine is predominantly released from neurons 2. epinephrine is predominantly released from the adrenal medulla
What is the relationship between organs with rich autonomic innervations and NE secretion? What are examples of organs rich in autonomic innervations?
1. Norepinephrine is secreted at synapses of postganglionic sympathetic nerves in organs with rich autonomic innervations: 2. the heart, salivary glands, vascular smooth muscle, liver, spleen, kidneys, and muscles
What kind of tumors arise in chromaffin cells? What do these tumors result in? What are paragangliomas?
1. Pheochromocytomas are chromaffin cell tumors 2. that result in irregular and excessive release of catecholamines; 3. paragangliomas are extra-adrenal chromaffin cell tumors
What diseases lead to the irregular increase of levels of catecholamines?
1. Pheochromocytomas, neuroblastomas, and adrenal medulla hyperplasia (non-tumor) can irregularly increase levels of catecholamines
What stimulates the production and release of epinephrine (E) and norepinephrine (NE)?
1. Sympathetic neurons release Ach--> stim. production of E/NE
What is the precursor for the catecholamines? Where is it derived from/ synthesized in?
1. Tyrosine 2. From food and it is made from phenylalanine in the liver
Alpha2 type adrenergic receptors stimulate what pathway? what parts of the body are activated by Alpha 2 type receptors? What does this activation result in? What are agonists of alpha2- adrenergic used for clinicall?
1. α2-adrenergic receptors stimulate the Gi pathway 2. Activation in CNS & vascular smooth muscle 3. Inhibition of norepinephrine as negative feedback, Centrally induced sedation, Inhibition of insulin from pancreas 4. Agonists of α2-adrenergic receptors are used as anesthesia for sedative effects, muscle relaxation, and analgesia; antagonists are antihypotensives
Beta 1-Adrenergic receptors stimulate what pathway? What parts of body are activated? How are these receptors utilized to treat disease?
1. β1-adrenergic receptors stimulate the Gs pathway 2.Activation in heart, kidney, and adipose tissue 3. Increased cardiac output and renin release, T3 increases the total number of cardiac β1 receptors, Increased lipolysis in adipose tissue, In nerve cells, increases nerve conduction velocity 4. Selective β-blockers block the action of β1 receptors and are used as antihypertensives; can help with heart failure if used as agonist
Beta-2 adrenergic receptors stimulate what pathways? What do they activate in the body? What are the physiological effects? What do agonists help with?
1. β2-adrenergic receptors stimulate the Gs and Gi pathways 2. Activation in smooth muscles, heart, veins, liver, and bronchi 3. Increased relaxation (vasodilation) in smooth muscles of arterioles, veins, and bronchi, Increased cardiac rate and contraction in the heart like β1 receptors, Increased serum glucose 4. Agonists can help with asthma & premature labor; nonselective β-blockers block both β1- and β2-adrenergic receptors to as antihypertensives
What pathways do Beta-3 adrenergic receptors stimulate? What parts of body are activated? What is the effect of Beta-3 activation? How are agonists used clinically?
1. β3-adrenergic receptors stimulate the Gs and Gi pathways 2. Activation in adipose tissue, gallbladder, colon, central nervous system, and the heart 3. Increased energy expenditure and intestinal motility, Increased lipolysis in adipose tissue, Increased thermogenesis in skeletal muscle 4. Agonists of β3-adrenergic receptors are used to treat an overactive bladder; antagonists can be used to block hyperthemia
what systems are the medulla and paraganglia a part of?
ANS/SNS
What are the hormones that are used by the PSNS?
Acetylcholine
What stimulates production of norepinephrine & epinephrine from the adrenal medulla and how are these hormones released?
Ach from being released from sympathetic neurons binding to nAchR stimulates production of E/NE--> E/NE are released via exocytosis in vesicles
E/NE production pathway
Ach released from vesicles in synapse--> binds to nAchR on chromaffin cells--> linked to Na+ gate-- > Causes membrane depolarization--> triggers AP to activate VG Ca2+ channels (VOCC)--> Increased Ca2+ triggers release of vesicles containing epinephrine MAINLY and NE to outside of cell= HORMONE REG.
What are the 5 main types of adrenergic receptors that NE and E can bind to? Which one(s) preferentially bind NE, and which ones prefer E?
Alpha 1,2 Beta 1,2,3 adrenergic receptors - Alpha1- NE -Alpha 2- NE -Beta 1- NE=E Beta 2- E Beta 3- NE
Epinephrine, norepinephrine, and dopamine are all.....
Catecholamines
In general w/NE and E you see: Smooth Muscle
Increase in: 1. Contraction (alpha 1) 2. Relaxation (Beta-2)
In general w/NE and E you see: Metabolism
Increase in: 1. O2 consumption (beta-1) 2. Heat and Lipolysis (Beta) 3. Glucose (alpha1 and beta 2)
In general w/NE and E you see: Cardiovascular
Increased: 1. HR 2. BP 3. Cardiac output
What innervates chomaffin cells (paraganglia) of the adrenal medulla?
Sympathetic preganglia innervate chomaffin cells
What are the symptoms of irregularly increased levels of catecholamines?
Symptoms= Hypertension Excessive sweating Headache Rapid heartbeat Tremors Shortness of breath
Summery slide
The adrenal medulla and paraganglia are part of the autonomic/sympathetic nervous system (SNS), which coordinates the body's automatic fight-or-flight response The adrenal medulla contains chromaffin cells that are responsible for secreting mainly epinephrine and smaller amounts of norepinephrine (NE is mainly produced in neurons) Preganglionic sympathetic neurons release acetylcholine to stimulate the production and release of epinephrine (mainly) and norepinephrine from granules in chromaffin cells Tyrosine is the precursor for synthesis of the catecholamines: dopamine, norepinephrine & epinephrine NE and E bind to α/β-adrenergic receptors located on various tissues and function to generally increase heart rate, blood pressure, and cardiac output in addition to different smooth muscle and metabolic effects Pheochromocytomas, neuroblastomas, and adrenal medulla hyperplasia (non-tumor) can irregularly increase level of catecholamine secretion
What is the direct link between cortisol and E expression?
The greater the cortisol the greater expression of PNMT and greater E expressed
