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81 Cards in this Set
- Front
- Back
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NE is the neurotransmittor of the?
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postganglionic sympanthetic neurons
interacts with pre & postsynaptic adrenergic receptors |
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NE & Epi are released from?
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from adrenal medulla as neurohormones
also some from in neurons of CNS |
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what is the basic structure of a catechol?
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benzene with 2 OH groups that are ortho to each other
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class of NE and Epi
state of NE & Epi at physiologic pH |
catecholamines
cations (+NH3) |
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what is the difference between NE and Epi?
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nor - w/o methyl on N
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which enantiomer of the catecholamines has biological activity?
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R enantiomer
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a catechol will be oxidized into what?
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ortho-quinone
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how do you stabilize catecholamine drugs?
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adding antioxidants such as ascorbic acid or sodium metabisulfite
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NE and Epi are synthesized from what aa?
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l-tyrosine
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give the order of steps in the synthesis of epi from the beginning
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l-tyrosine -> L-DOPA -> dopamine -> NE -> Epi
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what inhibits tyrosine hydroxylase
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incr concen of epi, NE, DA
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which form of tyrosinehydroxylase is active?
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the phosphorylated form
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what is the methyl donor is the synthesis of epi from NE?
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s-adenosyl methionine
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when NE is released into the synaptic cleft, what 4 events can occur?
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it will stimulate effector cell
it can be taken up by adregergic neuron (stored or metabolized) it can stimulate alpha2 receptors it can diffusion into the general circulation |
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how much of NE is taken back into the adreergic neuron by the uptake-1 system?
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95%
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the uptake-1 system can be inhibited by? what is the result of this?
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tricyclic antidepressants
cocaine more NE is left in the synaptic cleft - repeatedly stimulate adrenergic receptors |
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what is the final molecule that results from the biotransformation of NE & Epi
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3-methoxy-4-hydroxymandelic acid aka vanillyl mandelic acid
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what is pheochromocytoma?
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cancer of the adrenal medulla (more NE & Epi is produced, incr VMA)
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what is vanillyl mandelic acid a biomarker for?
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catecholamine turnover (incr VMA, incr turnover)
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both MAO and COMT occur in all tissues (ubiquitous), but what is the cellular location of each?
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MAO - outer membrane of mitochondria
COMT - cytoplasm however, only MAO is present in neurons! |
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what are the steps in the extraneuronal biotransformation of NE/Epi?
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NE/Epi
↝ 1. MAO 2. aldehyde dehydrogenase 3,4-dihydroxymandelic acid ↝ COMT 3-methoxy-4-hydroxymandelic acid |
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what are the steps that occur in the adrenergic neuron in the biotransformation of NE & Epi
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NE, Epi
MAO 3,4-dihydroxyphenyl-glycolaldehyde aldehyde reductase 3,4-dihydroxyphenylethylene glycol COMT 3-methoxy-4-hydroxyphenylethylene gylcol alcohol dehydrogenase aldehyde dehydrogenase 3-methoxy-4-hydroxymandelic acid |
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what are the 2 subtypes of adrenergic receptors
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alpha & beta
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what is the general structure of a adrenergic receptor?
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7 transmembrane helical structure coupled to G-proteins
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what does the G-protein Gi do?
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inhibition of adenylyl cyclase
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what does the G-protein Gq do?
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stimulation of PLC
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what does the G-protein Gs do?
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activation of adenylyl cyclase
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alpha-1 adrenergic receptors are coupled to
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Gq proteins
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alpha-2 adrenergic receptors coupled to
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Gi
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beta adrenergic receptors coupled to
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Gs
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which receptors are post-synaptic receptors?
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alpha-1
beta-1 beta-2 |
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what do the post-synaptic receptors do?
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mdiate organ/tissue responses of NE & Epi
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which receptor is pre-synaptic?
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alpha-2
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what do the pre-synaptic receptors do?
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modulate the quantity of NE in the synaptic cleft
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give the aa that aid in binding NE to the receptor
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Ser 204
Ser 267 Phe 290 Asn Asp 113 |
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how does Serine aid in the binding of NE to the receptor?
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provides hydrogen bonding with 2 OH groups (transmemembrane domain 5)
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how does Phenylalanine aid in the binding of NE to the receptor?
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hydrophobic interaction with phenyl ring
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how does Aspartate aid in the binding of NE to the receptor?
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ionic interaction (TMD 3)
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what is isoproterenol?
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a catechol that is not endogenous
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with regards to size, describe the alpha and beta adrenoceptors
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alpha - small space at receptor
beta - larger space, can accommodate bulky sidechains |
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rank the binding affinity of the catechols to alpha adrenoceptors
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NE > Epi > Isoproterenol
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rank the binding affinity of the catechols to beta adrenoceptors
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isoproterenol > Epi > NE
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what is the difference bewteen beta-1 and beta-2 binding of Epi & NE
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beta-1 binds Epi & NE with the same affinity
beta-2 binds Epi more strongly than it does NE |
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adrenoceptor subtype in the heart
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beta-1
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adrenoceptor subtype in the lungs
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beta-2
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adrenoceptor subtype in the arterioles & vascular smooth muscle
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alpha-1
beta-2 (& alpha) |
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adrenoceptor subtype in the eyes
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alpha-1
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adrenoceptor subtype in the liver
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alpha-1
beta-2 |
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adrenoceptor subtype in the intestine
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alpha-1
beta-2 |
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adrenoceptor subtype in the kidney
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beta-1
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adrenoceptor subtype in the uterus
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alpha-1
beta-2 |
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response of the heart to adrenoceptor stimulation
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incr conduction velocity, force & rate of contraction (incr cardiac output)
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response of the lungs to adrenoceptor stimulation
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relax in tracheal & bronchial smooth muscles (bronchodilation)
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response of the arterioles & vascular smooth muscle to adrenoceptor stimulation (alpha-1)
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constriction of most peripheral vasculature (cerebral, cutaneous, mucous membrane, visceral)
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response of the arterioles & vascular smooth muscle to adrenoceptor stimulation (beta-2)
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dilation of skeletal muscle vasculature
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response of the eyes to adrenoceptor stimulation
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constriction of radial muscle (pupil dilation)
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response of the liver to adrenoceptor stimulation
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incr gluconeogenesis & glycogenolysis
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response of the intestine to adrenoceptor stimulation
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decr motility
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response of the kidney to adrenoceptor stimulation
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incr renin production
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response of the uterus to adrenoceptor stimulation (alpha-1)
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contraction
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response of the uterus to adrenoceptor stimulation (beta-2)
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relaxation
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adrenoceptor subtype located in the adipocytes
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beta-3
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adrenoceptor subtype located in the CNS
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alpha-2
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response of the adipocytes to adrenoceptor stimulation
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incr lipolysis
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response of the CNS to adrenoceptor stimulation
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reduced sympathetic outflow
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drugs that affect the biosynthesis of Epi & NE
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metyrosine
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drugs that affect the storage of Epi and NE
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reserpine
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durgs that affect the release of Epi and NE
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guanethidine
guanedrel |
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what is the brand name for metyrosine?
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demser
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what is the brane name for reerpine?
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serpasil
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brane name for guanethidine
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ismelin
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brand name for guanadrel
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hylorel
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what is the MOA of metyrosine?
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it inhibits tyrosine hydroxylase, decr the biosynthesis of Epi and NE
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uses for metyrosine
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to manage pre-operative pheochromocytoma
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reserpine is isolated from what indian shrub?
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raulwofia serpentina
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MOA of reserpine
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inhibits transport of NE from cytoplasm into storage vehicles
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what is the onset of action of reserpine?
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works by depleting NE stores - takes time to diminish NE pool - slow onset
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what is the duration of action of reserpine?
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long lasting because there is no new NE being stored in the vesicles
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reserpine is used to treat
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severe hypertension
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MOA of guanethidine & guanadrel
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enter the neuron by uptake-1 process where they stabilizw the storage vesicle membrane to inhibit release of NE
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half life and bioavailability of guanethidine & guanadrel
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guanethidine
half life: 5 days bioav: 5% guanadrel half life: 12 hours bioav: 85% |
