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125 lecture 4
transmitter and receptors
19
Anatomy
Undergraduate 1
04/26/2013

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Term
a catechol group is a phenol group with -OH attached in which two positions?
Definition

3 and 4. 

catechlamines are synthesised from tyrosine and these include noradrenaline, adrenaline and dopamine. the brain lacks phenyalanine hydroxylase. it converts Phe to Tyr thus Tyr is transported into the brain from blood

Term

dopamine is associated with motor function and is lost in which disease?

 

which enzymes are involved in catabolism of catecholamines?

Definition

Parkinson's disease.

 

catabolism involves monoamine oxidase (MAO) and catechol 0-methyltransferase (COMT)

Term
Parkinson's was first described in 1817 by J parkinson. the mean age of onset is ~60. it is characterised by 3 main symptoms: muscle rigidity, tremor and bradykinesia. what is bradykinesisa?
Definition

slowness of movement.

 

this is a multifactorial dsease involving age, environmental factors and genetics.

 

Term
PD is due to degeneration of pigmented cells of which region in thebasal ganglia?
Definition

substantia nigra pars compacta

(shit thats a mouthfull)

 

as substantia nigra specifially uses dopamine, PD results in >50% depletion of this transmitter

Term
why must we use L-dopa and not dopamine itself to alleviate symptom of PD?
Definition
because dopamine cannot cross the blood brain barrier but L-dopa can. so it is transported into the brain then turned into dopamine.
Term
how is metabolism of L-dopa to dopamine prevented in the periphery?
Definition

by a simultaneous admnistration of a Dopa decarboxylase inhibitor which cannot penetrate the blood-brain barrier.

 

also inhibitors of MAO and COMT can be given to inhibit dopamine degradation.

 

PD patients are usually given a cocktail of L-dopa, DDI, MAO and COMT

Term

serotonin (5-HT) is synthethised from tryptophan by which two enzymes?

 

how many different types of receptors does it bind to?

Definition

tryptophan hydroxylase and 5-hydroxytryptophan (5-HTP) decarboxylase.

14 different types of receptors

Term

in ralation to serotonin, what affect do hallucegenic drugs such as LSD have?

 

the action of serotonin can be terminated mainly by reuptake from the synapse via the 5-HT reuptake transporter on the presynaptic neuron. what else can inactivate the action?

Definition

they act as 5-HT agonists and mimick the action of serotonin at 5-HT2A receptors.

 

serotonin action can also be terminated by MAO.

Term

true or false?

amino acids are present at a higher concentration (30mM) than in any other body tissue

Definition

true.

these are all non essential amino acids made in situ from glycolytic and citric acid cycle intermediates.

 

dicarboxylic amino acids glutamate and aspartate are excitatory whereas glycine and GABA are inhibitory


Glutamate and GABA are major transmitters in the brain.

Term
the most common type of neurotransmitter in the h........ are peptide transmitters. they are synthesised as large precursor p...... then transported to synaptic release site and activated by proteolytic c........
Definition

hypothalamus, proteins, cleavage

 

peptide transmitters have slow potsynaptic effects and their actions are terminated by extracellular proteases. they are often co-released with other transmitters. includes opioids - endophins, enkephalins and dynorphins

other examples are substance P, neurotensin, vasoactive intestinal peptide (VIP)

Term
other transmitters include purines (ATP,GTP and others) Histamine and gases such as Nitric Oxide. NO is not stored in synaptic vesicles as it is a gas but instead is made when required by NOS from arginine. how do NO propagate and terminate?
Definition

it diffuses from nerve terminals inot adjacent cells forming covalent linkages to a multiplicity of targets, which maybe enzymes or other targets. 

inactivation presumably involves diffusion away.

Term
describe the 2 main types of transmitter receptors
Definition

ionotropic receptor - fast, few milliseconds and always stimulatory - transmitter acts directly on a ligand gated ion channel to open the channel

 

metabotropic receptor - slow up to hours, can trigger opening/closing of a seperate ion channel and also other effects on cell - acts indirectly on a GPCR

Term
which one is a direct and which is an indirect receptor from nicotinic and muscarinic receptors?
Definition

nitotinic is direct

 

muscarinic is indirect and has five subtypes

M1,M2,M3,M4,& M5

Term

how a G protein acts indirectly on an ion channel. A...... binds to receptor. GTP exchnages for G.... on the a...... subunit. G protein dissociates from receptor with its 3 subunits also doing the same. the aplha subunit activates the ion channel. it is inactivated by h....... of G..... to G.....

the 3 subunits recombine and attach to the receptor which can bind another agonist

Definition
agonist, GDP, alpha, hydrolysis, GTP, GDP
Term

some g proteins can stimulate or inhibit enzyme targets instead of acting on ion channels. the most common of these tragets are the enzymes: adenylate cyclase, guanylate cyclase and phospholipase C.

what are the corresponding second messengers?

Definition

adenylate cyclase = cyclic AMP or cAMP

guanylate cyclase = cyclic GMP or cGMP

phospholipase C = Inositol triphosphate and diacylglycerol

 

these can then cause a slow response in the cell 

Term

structure of ligand gated receptors -composed of 4 or 5 different subunits arranged around a central pore. eg:nicotinic acetylcholine, GABAA, glycine, 5-HT3 receptors

nicotinic receptor has five subunits from a possible 17 thus there are many combinations that differ in skeletal muscle, autonomic ganglia,brain. the alpha subunit binds to acetylcholine resulting in a conformational change which opens the central ion channel.

Definition

structure of G protein coupled receptors


made from a single protein with 7 membrance spanning alpha helices = 7 transmembrane receptor (7TM)

eg: muscarinic acetylcholine, alpha-adrenergic and Beta-adrenergic receptors, all 5-HT receptors except 5HT3, rhodopsin, olfactory receptors and many others

Term

tricyclic antidepressants bblock noradrenaline and s.......... re-uptake

 

SSRIs are administered for d....... obsessive compulsive disorder and also block serotonin re-uptake

Definition

serotonin, depression

 

 

Term
valium and other benzodiazepines are administered for anxiety but how do they work?
Definition

they activate GABA receptors

 

MAO inhibitors are given for Parkinson's and depression. they block the breakdown of biogenic amines.

Term
what is the dopamine precursor used in Parkinson's disease to cross the blood-brain barrier?
Definition

L dopa

 

 

acetylcholinetransferase inhibitors are administered in Alzheimer's disease to block the breakdown of acetylcholine

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