Term
| ACh is formed in a single step process from... |
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Definition
ACh is formed in a single step process from choline and acetylcoenzyme A (Acetyl CoA)
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Term
Choline comes from... and Acetyl CoA comes from... |
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Definition
Choline comes mainly from fat in diet (choline containing lipids) or produced in the liver Acetyl CoA is generated w/in all cells by metabolis of sugars and fats |
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Term
Synthesis of ACh is catalyzed by..
Where is the enzyme present? |
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Definition
Synthesis of ACh is catalyzed by the enzyme choline acetyltransferase (ChAT)
Choline acetyltransferase is present in the cytoplasm of the cell, only in cholinergic neurons |
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Term
| ACh loaded into vesicles by |
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Definition
| ACh loaded into vesicles by vesicular ACh transporter |
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Term
Vesicular ACh transporter protein blocked by...
what are the effects |
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Definition
Vesicular ACh transporter protein blocked by vesamicol
Vesamicol decreases decreases vesicular ACh but increases amount of ACh in the cytoplasm of the terminal (when neuron fires, much less ACh is released) |
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Term
| Cause of these symptoms: muscle pain in abdomen and chest, tremors, nausea and vomiting, salivation and copious sweating |
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Definition
| Overactivity of of the cholinergic system (massive release of ACh in the PNS) |
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Term
ACh levels broken down by...
into... |
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Definition
| ACh broken down by acetylcholinesterase (AChE) into choline and acetic acid |
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Term
| AChE located...(3 places) |
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Definition
| AChE located in the presynaptic terminal, the postsynaptic membrane, and the neuromuscular junction (to allow muscles to relax after contraction) |
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Term
After ACh broken down, choline is taken up into...
if blocked by...then what is the effect? |
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Definition
After ACh broken down, choline is taken up into the cholinergic nerve terminal by a choline transporter.
if blocked by hemicholinium-3 (HC-3), the rate of ACh production decreases. |
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Term
True/false: HC-3 can cross the blood-brain barrier.
Effects of HC-3 injected directly into rat brain... |
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Definition
FALSE...HC-3 can NOT cross the BBB
If HC-3 injected directly into rat brain, rats show impaired performance on tasks requiring visual attention. |
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Term
| Myasthenia gravis causes... |
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Definition
| Myasthenia gravis causes body to develop antibodies against own neuromuscular cholinergic receptors |
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Term
| Why does PB (pyridostigmine bromide - Soman antidote) not cause adverse effects? |
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Definition
| Very low penetration across the BBB (but the BBB can be "opened up" under stress) |
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Term
| The rate of ACh synthesis is controlled by... |
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Definition
| The rate of ACh synthesis is controlled by precursor availability and cell firing |
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Term
| In the early stages of Parkinson's, why are some patients prescribed anticholinergic drugs (Norflex, Cogentin, Artane) instead of L-DOPA? |
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Definition
| B/c regulation of movement is largely dependent on the balance b/w ACh and DA in the striatum...this balance is messed up in Parkinson's patients (low DA) which contributes to the motor symptoms |
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Term
The Basal Forebrain Cholinergic System (BFCS) is a collection of cholinergic nerve cells that innervates...
damage this this system contributes to symptoms of... |
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Definition
The Basal Forebrain Cholinergic System (BFCS)is a collection of cholinergic nerve cells that innervates the cerebral cortex and limbic system structures.
Damage to the BFCS contributes to symptoms of Alzheimer's disease |
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Term
The cognition enhancing effects of ACh are due to stimulation of what receptors? |
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Definition
| Muscarinic ACh receptors are necessary for the cognitive enhancing effects of ACh. |
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Term
| The two ACh receptor subtypes |
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Definition
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Term
Nicotinic receptors respond selectively to the agonist...
and Muscarinic receptors are stimulated selectively by.. |
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Definition
Nicotinic receptors respond selectively to the agonist nicotine
Muscarinic receptors are stimulated selectively by muscarine |
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Term
| Where are nicotinic receptors highly concentrated? |
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Definition
| Nicotinic receptors are highly concentrated on muscle cells at neuromuscular junctions, on ganglionic neurons of the sympathetic and parasympathetic system, and on certain neurons in the brain |
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Term
| Nicotinic receptor response to binding of ACh |
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Definition
| Nicotinic receptor (ionotropic) opens, allowing Na+ and Ca2+ ions to enter (depolarizing and exciting the cell) |
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Term
| True/False: Nicotinic receptors mediate fast excitatory responses in both the CNS and PNS |
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Definition
| TRUE: Nicotinic receptors mediate fast excitatory responses in BOTH the CNS and PNS |
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Term
| True/False: both active sites on nicotinic receptors must be bound to ACh in order to be activated |
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Definition
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Term
| muscle nicotinic receptors are less sensitive than neuronal nicotinic receptors...if they weren't... |
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Definition
| smokers would experience muscle contractions and spasms during smoking |
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Term
| When nicotinic receptors are subjected to continuous agonist exposure, they experience... |
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Definition
| Desensitization - channel remains closed, regardless of whether molecules of an agonist (such as ACh or nicotine) are bound to the receptor |
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Term
| True/False: After a while, desensitized nicotinic receptors spontaneously become resensitized |
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Definition
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Term
| State in which the resting potential of a membrane is lose and the cell cannot be excited until the agonist is removed and the membrane repolarized |
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Definition
| Depolarization Block - cause by the few active receptors (while the others are desensitized) that produce persistent depolarization |
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Term
| State in which the resting potential of a membrane is lost and the cell cannot be excited until the agonist is removed and the membrane repolarized |
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Definition
| Depolarization Block - cause by the few active receptors (while the others are desensitized) that produce persistent depolarization |
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Term
| How does succinylcholine work as a muscle reactant if it is a chemical relative to ACh? |
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Definition
| Succinylcholine is resistant to AChE, thus it continuously stimulates the nicotinic receptors and causes a depolarization block |
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Term
| M5 muscarinic receptors thought to selectively influence... |
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Definition
| M5 muscarinic receptors thought to selectively influence the addictive properties of opiate drugs |
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Term
| Outside of the brain, muscarinic receptors are found in high densities in... |
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Definition
| the cardiac muscle of the heart and in smooth muscles associated with many organs |
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Term
| Important mechanism of muscarinic receptors is the opening of... |
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Definition
| K+ channels (causing hyperpolarization) |
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Term
| Peripheral muscarinic receptors are activated by ACh released by... |
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Definition
postganglionic fibers of the parasympathetic nervous system
(muscarinic receptor activation causes decrease of heart rate, but increase in smooth muscle activity (rest and digest) and increased secretory responses) |
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Term
| Difference b/w parasympathomimetic agents and parasympatholytic agents |
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Definition
Parasympathomimetic agents are muscarinic receptor agonists and over-excite actions of the parasympathetic system
Parasympatholytic agents are muscarinic receptor antagonists and inhibit actions of the parasympathetic system |
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Term
| The two varieties of tobacco and where they were found |
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Definition
Large-leaf variety: Nicotiana Tabacum (South America)
Small-leaf variety: Nicotiana Rustica (North America) |
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Term
| The principal metabolite of nicotine |
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Definition
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Term
How much nicotine does the typical cigarette contain?
How much actually reaches the bloodstream of the smoker? |
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Definition
6-11mg of nicotine in the typical cigarette
Only 1-3mg if of it reaches the smoker's bloodstream |
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Term
| True/False: arterial nicotine concentrations rise more rapidly and reach a greater peak than the concentrations of nicotine in venous blood |
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Definition
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Term
| Nicotinic metabolites excreted mainly... |
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Definition
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Term
| Peripherally, high affinity nAChRs are found in the ganglia of... |
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Definition
| Peripherally, high affinity nAChRs are found in the ganglia of the autonomic (para and sympathetic) nervous system |
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Term
| High affinity nAChRs are made up of... |
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Definition
| 2 alpha and 3 beta subunits |
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Term
| nAChRs that are located on the presynaptic neuron function to... |
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Definition
| enhance neurotransmitter release |
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Term
| Biphasic effect of high doses of nicotine |
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Definition
| High doses of nicotine begin by stimulating nicotinic cholinergic functions but then turns to a nicotinic receptor blockade (accounts for nicotine poisoning) |
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Term
| Relaxing and calming effects of nicotine due to... |
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Definition
| relief of withdrawal symptoms...non-smokers experience nausea, dizziness, and heightened tension. |
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Term
| True/False: nicotine shortens reaction time of only smokers, not non-smokers. |
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Definition
| FALSE...nicotine injections shorten reaction time of both smokers and non-smokers |
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Term
| Effect of nicotine on beta2 knockout mice |
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Definition
| no effect seen. wildtype showed enhanced cognitive retention - beta2 knockout mice showed no effect, suggesting beta2-alpha4 may be critical for the memory-enhancing effects of nicotine |
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Term
| Do mice readily self-administer nicotine? |
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Definition
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Term
| This pathway from...to the...plays a key role in nicotine's reinforcing effects |
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Definition
| The mesolimbic DA pathway from the VTA to the nucleus accumbens plays a key role in nicotine's reinforcing effects |
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Term
Smoking a cigarette causes the adrenal medulla to release...
which lead to... |
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Definition
| Smoking a cigarette causes the adrenal medulla to release E and NE which lead to mild physiological arousal like increased heart rate and blood pressure |
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Term
| Nicotine actions of the parasympathetic nervous system |
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Definition
| increases hydrochloric acid secretion in the stomach and muscle contractions in the bowel |
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Term
The first cigarette of the day being the
"best one" is due to... |
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Definition
| Acute tolerance throughout the day |
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Term
The first cigarette of the day being the
"best one" is due to... |
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Definition
| Acute tolerance throughout the day |
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Term
| True/False: Long-term nicotine exposure causes chronic tolerance |
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Definition
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Term
| Nicotine abstinence syndrome is mediated by... |
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Definition
| nicotine abstinence syndrome is mediated by nicotinic receptors in both the central and peripheral nervous systems |
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Term
| The central component of nicotine withdrawal may involve receptors in... |
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Definition
| The central component of nicotine withdrawal may involve receptors in the VTA |
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Term
| When VTA nicotinic receptors are activated, they stimulate... |
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Definition
| When VTA nicotinic receptors are activated, they stimulate DA cell firing and DA release in the nucleus accumbens |
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Term
Nicotine resource model
vs.
deprivation reversal model |
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Definition
Nicotine resource model is the hypothesis that people smoke in order to control mood and enhance concentration
The deprivation reversal model is the hypothesis that these positive effects are only due to the alleviation of withdrawal symptoms (smoking increases overall stress) |
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Term
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Definition
| Non-dependent smokers that smoke a few cigarettes a day |
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Term
| PET scans showed that in smokers, compared the non-smokers, there is a large reduction in... |
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Definition
| both monoamine oxidases - MAO-A and MAO-B |
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Term
MAO enzymes play a critical role in...
What does this say about the inhibition of MAO-A and MAO-B in smokers? |
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Definition
| MAO enzymes play a critical role in metabolizing DA...shows that nicotine not only causes DA release, but also slows its breakdown |
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Term
| Caffeine absorption begins in the...but occurs mainly in... |
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Definition
| Caffeine absorption begins in the stomach but occurs mainly in the small intestine |
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Term
| Average half-life of caffeine |
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Definition
| Average half-life of caffeine= 4 hours |
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Term
The biphasic effects of caffeine in rodents (at low and high doses)
...different in humans? |
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Definition
Low doses: stimulant effect - increased locomotor activity
High doses: opposite - reduced activity
High doses in humans results in anxiety and tension |
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Term
| Peripheral physiological effects of caffeine |
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Definition
| increased blood pressure and respiration rate, enhanced water secretion (diuresis) and stimulation of catecholamine release (particularly E) |
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Term
| Most important clinical use of caffeine |
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Definition
| Treatment of newborns who show apneic episodes (periodic cessation of breathing) |
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Term
| True/False: Caffeine directly influences catecholamine systems in the manner of psychomotor stimulants amphetamine and cocaine. |
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Definition
| FALSE...it is clear that caffeine does NOT directly influence catecholamine systems in the same manner as amphetamine and cocaine |
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Term
| Caffeine-induced behavioral stimulation caused by... |
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Definition
| Caffeine-induced behavioral stimulation caused by the blockade of adenosine receptors (caffeine most potently blocks A1 and A2A receptor subtypes) |
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Term
| The fly agaric mushroom is a source of...(3 things) |
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Definition
| the fly agaric mushroom is a source of muscarine, the GABA-A agonist muscimol, and excitotoxin ibotenic acid |
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Term
| 4 functions of the muscarinic ACh receptors, M1, M3, and M5 |
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Definition
Increase activity of PLC-Beta
Increase [Ca2+]
Increase activity of MAP kinases
Decrease M current |
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Term
| 4 functions of the muscarinic ACh receptors M2 and M4 |
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Definition
Decreased activity of adenylyl cyclase
and activity of voltage-gated Ca2+ channels
Increased activity of MAP kinases and GIRK channels |
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Term
| The 5 types of mAChRs serve various functions in what system? |
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Definition
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Term
| mAChRs are involved in the regulation of.. |
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Definition
| mAChRs are involved in the regulation of dopamine |
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Term
| Dried tobacco leaves contain about __% nicotine |
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Definition
| Dried tobacco leaves are ~6% nicotine |
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Term
| True/False: 1/3 of the world adult population smokes (>1.1 billion people) |
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Definition
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Term
How many people does tobacco kill a year?]
How many years of life does the average smoker lose?
What percentage of all lifetime smokers die prematurely b/c of cigarette induced disease? |
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Definition
>5 million per year
Average smoker dies 14 years sooner
50% of all lifetime smokers die prematurely due to cigarette induced disease |
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Term
How many cigarettes does the average regular smoker smoke a day?
What do you call people who smoke <5 a day? |
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Definition
Average regular smoker smokes ~25 cigarettes a day
Those who smoke <5 a day are called "chippers" |
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Term
| Why is smoking sometimes called a pediatric disorder? |
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Definition
| Because the majority of smoking is initiated during adolescence |
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Term
| Most routes of administration can produce effective absorption of nicotine with the exception of... and why? |
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Definition
| swallowing...nicotine is a weak base (pka~8) and the first pass effect is very strong |
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Term
| Of rats given nicotine over 5, 10, and 100 seconds, which displayed the highest amount of locomotor activity after being infused for 6 days? |
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Definition
| The rats given nicotine for 5 seconds (behavioral sensitization |
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Term
| Nicotine causes the c-fos protein to be expressed in... |
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Definition
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Term
| The lethal dose of nicotine for adult humans |
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Definition
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Term
| Possible reason for why there are so few pure nicotine abusers |
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Definition
| the toxicity - smoking allows better control of dose |
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Term
| How does the nicotine kill? |
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Definition
| By creating a depolarization block of muscles involved in the respiratory system (like with nerve gas weapons) |
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Term
| A high dose of nicotine produces unpleasant symptoms largely due to actions of nicotine on... |
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Definition
| the autonomic nervous system |
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Term
| People with reduced nicotine metabolism (or less cytochrome P450 2A6) are more or less likely to become smokers? |
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Definition
| Less nicotine metabolism= less likely to become a smoker |
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Term
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Definition
| Methoxsalen is a drug that inhibits cytochrome P450 2A6 -> experience the unpleasant effects of nicotine at lower doses because the metabolism of nicotine is inhibited |
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Term
| What are the effects of nicotine on performance on attention-demanding tasks in smokers vs. non-smokers |
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Definition
| Performance is improved in smokers and non-smokers when given nicotine, but the performance of smokers with nicotine is only as good as non-smoker without nicotine |
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Term
| Experienced drug users will sometimes misidentify IV nicotine with... |
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Definition
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Term
| The success rates of quitting smoking can be compared to... |
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Definition
| the success rates of quitting heroin...VERY LOW |
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Term
| Systemic nicotine increases activity of... |
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Definition
| Systemic nicotine increases activity of midbrain DA cells (changes their pattern of firing to a "burst" mode, that produces more DA release at terminals in the striatum) |
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Term
| What is required for nicotine self-administration? |
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Definition
| NAc dopamine is required for nicotine self-administration |
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Term
| Most common nAChR in the CNS is... |
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Definition
| Most common nAChR in the CNS is alpha-4-beta-2* |
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