On this page, is a study guide for Stahl's chapter 1, 2 and 3 practice questions on transporters and neurotransmission. The guide has been made from the 5th edition Test Bank for Stahl's Essential Psychopharmacology Neuroscientific Basis and Practical Applications by Stephen M. Stahl
1. retrograde neurotransmission: A method of neurotransmission in which the postsynaptic cell communicates with the presynaptic neuron.
2. function of chemical neurotransmission: presynaptic genome converse with a postsynaptic genome: DNA to DNA, presynaptic command center to postsynaptic command center and back p. 10
3. Nitric Oxide (NO), Nerve Growth Factor (NGF), and Endocannabinoid (EC) use _________________: retrograde transmission p. 6
4. Nitric Oxide (NO) is synthesized postsynaptic and then diffuses out to a: presynaptic membrane to interact with cyclic guanosine monophosphate sensitive targets p. 6
5. nerve growth factor (NGF) is released from postsynaptic sites and diffuses to a: presynaptic neuron, where it is take up into vesicles and transported to the cell nucleus via retrograde systems to interact with the genome p.6
6. endocannabinoid (EC) is synthesized postsynaptically and diffuse to: presynaptic cannabinoid receptors, such as CB! or cannabinoid 1 receptor p. 6
7. volume neurotransmission - chemical messengers spill over to distant synapses by diffusion: Neurotransmission without a synapse, called "Chemical Puffs" , the brain is a sophisticated chemical soup p.6-7
8. volume transmission is: NONsynaptic diffusion neurotransmission p. 6-7
9. volume neurotransmitter release can also occur on: monoamine autoreceptors , there is no synapse at the somadentritic autoreceptors p. 8
10.striatum: Dopamine (DA) reuptake pumps are abundant in the
11.the prefrontal cortex: example of where volume neurotransmission occurs due to limited Dopamine reuptake receptors p. 8
12.12 process by which electrical impulse is converted to chemical signal at the synapse. this is how the neuron transduces an electrical stimulus into a chemical message.: Excitation-secretion coupling p.8-9
13.electrical impulses open: voltage-sensitive sodium channgels (VSSCs) and voltage-sensitive calcium channels (VSCCs) p. 9
14.signal transduction cascade: initial event occurs quickly, but 2, 3, 4th order messengers may take days to weeks to work. each step represent an opportunity for something to go right or wrong. each of the signal messenger systems send message from extracellular to intracellular via a second messenger p. 10
15.ligand-gates ion, channels, ionotropic receptors, and ion-channel-linked receptors are opened by: neurotransmitters p. 52
16.ligand-gated ion channels are also a: type of receptor p.54
17.voltage-sensitive or voltage-gated ion channels are opened by: a charge or voltage across the membrane p. 52
18.Voltage-sensitive sodium ion channel: 1. subunit of a pore forming protein with six transmembrane segments
19.2. Transmembrane segment #4 detects the difference in charge 3. each subunit of a voltage-sensitve ion channel has an extracellular amino acid loop between transmembrane segments 5 & 6 and located on the outside of the pore
20.4. On the connector loop between the 3rd and 4th subunits, amino acid act like a plug p.68
21.ionic filter that allow only sodium (VSSC) or calcium (VSCC) through: transmembrane segments 5 & 6 act as an p.68
22.voltmeter to alert the rest of the protein to begin conformational changes of the ion channel to either open or close: transmembrane segment 4 functions like a
23.voltage-sensitive calcium ion channel: 1. subunit of a pore forming protein with six transmembrane segments
24.2. Transmembrane segment #4 detects the difference in charge 3. each subunit of a voltage-sensitve ion channel has an extracellular amino acid loop between transmembrane segments 5 & 6 and located on the outside of the pore
25.4. On the connector loop between the 2nd and 3rd subunits, work as a snare to hook up the presynaptic vesicles p.71
26.22. L, N, P/Q, R, T: subtypes of VSCC's p.73
27.23 G-protein-linked systems, ion-channel-linked systems, hormone-linked systems, and neurtrophin-linked systems are: four of the most important signal transduction cascades in the brain p. 11, 12
28.the G protein-linked and ion-channel-linked cascades are trigger by: neurotransmitters p.11
29.intracellular second messenger: Each of the four signal transduction cascades passes its message from an extracellular first messenger to a p.11
30.First messenger of G-protein linked must first meet: four key elements p. 12
31.Phosphoproteins & genes: two major targets of signal transduction p.13
32.methylation and deacetylation of histones: silence genes p.24
33.demythylation and acetylation of histones: activate genes p.24
34.compresses chromatin, thereby silencing the gene expression: methylation and deacetylation of histones p.24
35.decompresses chromatin, thereby activating the gene expression: demythylation and acetylation of histones p.24
36.what enzyme try to maintain status quo of a cell?: DNA methyl-transferase 1 p. 26
37.why would DNA methyl-transferase 1 want maintain the status quo of a cell?: to keep a neuron a neuron, a liver cell a liver cell p.26
38.Vesicular monamine transporters 1 and 2 (VMAT1, or VMAT2): transports serotonin, norepinephrine, dopamine, and histamine p.29
39.Vesicular acetylcholine transporter (VAChT): transports acetylcholine p.29
40.Vesicular inhibitory amino acid transporter (VIAAT): transports GABA p.29
41.Vesicular glutamate transporter (VGluT): transports glutamate p.29
42.SLC18 (VMATs), SLC32 (VIAATs), SLC17 (VGluT1-3): 3 Subclasses of INTRA-
43.CELLAR synaptic vesicle transporters p.29 , 32
44.SLC18 (VMATs): intracellar synaptic vesicle transports serotonin, norepinephrine, dopamine, histamine, and acetycholine p.29, 32
45.SLC32 (VIAATs),: intracellar synaptic vesicle transports GABA p.29
46.SLC17 (VGluT1-3): intracellar synaptic vesicle transports Glutamate p.29, 32 42. neurotransmitters can be transported into the synaptic vesicle, thereby keeping the charge inside the vesicle constant: proton pump pumps positively charged protons out of the synaptic vesicle so p.32 Figure 2-2B
47.SLC18 gene family: serotonin, norepinephrine, dopamine, and acetycholine belong to the p. 32, table 2-3
48.SLC32 gene family: GABA belongs to the p. 32, table 2-3
49.SLC17 gene family: Glutamate belongs to the p. 32, table 2-3
50.Glutamate transporters belong to a unique family: SLC1 p.33
51.47 Excitatory amino acid transporters 1-5: EAAT 1-5 uptake of glutamate into glia, where glutamate is converted into glutamine, and then glutamine enters the presynaptic to reconvert back to glutamate p.33
52.SLC6 PLASMA MEMBRANE transporter - sodium/chloride coupled transporters: Transports monoamines SE, NE, DA and GABA, Glycine p.29
53.two major subclasses of Plasma Membrane Transporters for neurotransmitters: 1. sodium/chloride coupled transmitters (solute carrier SLC6 gene family)
54.2. High -affinity glutamate transporters, (solute carrier SLC1 gene family) p.29
55.SERT (SLC6 Gene): reuptake Presynaptic transporter for serotonin p.30
56.SLC1 PLASMA MEMBRANE transporters 1-5: Transports Glutamate p. 30 Table 2-2
57.SERT (SLC6 Gene) false substrate: Ecstasy (MDMA) p.30
58.NET (SLC6 Gene): reuptake Presynaptic transporter for norepinephrine p.30
59.NET (SLC6 Gene) false substrate: Dopamine, epinephrine, amphetamine p.30
60.DAT (SLC6 Gene): reuptake Presynaptic transporter for dopamine p.30
61.DAT (SLC6 Gene) - false substrate: norepinephrine, epinephrine, amphetamine p.30
62.GAT: reuptake Presynaptic transporter for GABA p. 30
63.GABA has how many type of transmitters?: GAT1-4 p.33
64.a key presynaptic transporter of GABA is: GAT1 and is selectively blocked by the anticonvulsant tiagabine, thereby increasing synaptic GABA concentrations p. 33
65.an increase of synaptic GABA may also have: therapeutic action in anxiety, sleep disorder, and pain p.33
66.GlyT: reuptake Presynaptic transporter for Glycine p.30
67.EAAT: reuptake Presynaptic transporter for the Excitatory amino acid (glutamate) p.30
68.two types of neurotransmitter transport systems: presynaptic reuptake and vesicular storage p.p.29
69.Enzymes target: approximately 10% of psychotropic drugs p.29
70.Vesicular transporters fo acetylcholine (SLC18), GABA (SLC32 gene family), and glutamate (SLC17 gene family are NOT known to be targeted by: any drug utilized by humans p. 34
71.vesicular transporters for monoamines in the SLC18 gene family are: potently targeted by several drugs p.34
72.67 4-transmembrane-regions ligand-gated ION channel target: approximately 20% (1/5) of psychotropic drugs p.29
73.Pentameric subtype of ligand-gated ion channels: 4 transmembrane regions
74.+ 5 protein subunits come together to make p. 54
75.receptors on all five subtypes, both inside and outside: Pentameric subtype of ligand-gated ion channels p.54
76.Tetrameric subtype of ligand-gated ion channels: 3 full transmembrane regions and a 4th reentrant loop+ 4 protein subunits p. 56
77.receptors on all four subtypes, both inside and outside: Tetrameric subtype of ligand-gated ion channels p.56
78.tetrameric structure is typical of: glutamate receptors known as AMPA and
79.NMDA p.56
80.when a full agonist is present on a receptor, and a partial agonist is present, what happens to the partial agonist?: becomes a net antagonist p. 61
81.an agonist increases signal transduction from baseline, what does an inverse agonist do?: inverse agonist decreases below baseline levels, basically the opposite of an agonist action p. 63
82.desensitization is another state of the ligand-gated ion/receptor as a result of: prolonged exposure to agonist, and is suspected as a way for receptors to protect themselves p. 64
83.when an agonist is absent from a receptor and a partial agonist is present, what happens to the partial agonist?: becomes a net agonist p.61
84.7 transmembrane-region G-protein linked: approximately 1/3 of psychotropic drugs
85.another name for G-Protein-Coupled RECEPTORS (GPCRs) is: 7-transmembrane Receptors
86.GPCRs interact with: guanyl nucleotides (GDP, GTP)
87.The G-protein-linked system works though a cascade involving: cAMP
88.(cyclic adenosine monophosphate) and protein kinase A p. 12
89.The Ion-channel-linked system works through a cascade involving: calcium activates calcium/calmodulin-dependent protein kinase (CaMK) p.11
90.G proteins bind with: Guanosine Diphosphate (GDP) and Guanosine Triphosphate (GTP)
91.G protein-coupled receptors (GPCRs) belong to: a large family of integral membrane proteins involved in signal transduction; characterized by their 7 membrane-spanning alpha-helices; utilize heterotrimeric G protein to transmit signals to effector cells
92.12-transmembrane-region transport: approximately 1/3 of psychotropic drugs either by presynaptic reuptake and vesicular storage p.29
93.to aid the communication between a cell and its environment: best describes the role of the membrane receptor
94.a ligand: A molecule or ion that attaches to a receptor, triggering changes within the cell p. 52
95.lock and key theory (older theory): specific ligand that fits onto a specific receptor
96.which type of cell are ligand-gated ion channels most commonly found?-
97.: Cells that need to respond quickly to external stimuli p.54
98.resting, open, closed, desensitized, inactivated: five states of ligand-gated ion channels
99.work only in the presence of a neurotransmitter: allosteric modulators p. 66 91. if a neurotransmitter is not binding to its site, the PAM and the NAM: do nothing p.66
100. an example of a PAM are: benzodiazepine p. 66
101. an example of a NAM are: a benzodiazepine inverse agonist p. 67
102. when PCP or ketamine bind to a NAM site, they: prevent glutamate/glycine cotransmission from opening the channel
103. boosts what the neurotransmitter does: PAM (postive allosteric modulator) binds to its allosteric site p.66
104. blocks the neurotransmitter: NAM (negative allosteric modulator) binds to its allosteric site p.66
105. anxiolytics and hypnotics: type of drugs that respond quickly on ionotropic receptors p. 54
106. "stabilizers": another name for partial agonists p.61
107. ligand-gated ion channels are NOT the same as: voltage-gated channels rely only on a difference in membrane potential
108. concept of induced fit: ligands and receptors can change conformation slightly, thereby enhancing their bond (new theory)
109. What is NOT true regarding ligand-gated ion channels?: Open or close in response to deformations in the cell membrane
110. Causes dissociation of the ligand from the G-protein coupled receptor: -
111. Hydrolysis of GTP to GDP
112. Allows docking of intracellular proteins involved in signal transduction: Once phosphorylated, the intracellular segment of a receptor tyrosine kinase (RTK) 104. In the scenario of adrenaline interaction with its G-protein coupled receptor, what functions as a second messenger?: Cyclic AMP p.12
113. cancers: Mutations in the Receptor Tyrosine Kinases (RTK) would most likely be associated with
114. CREB =: cAMP Response Element Binding protein, a transcription factor in the cell nucleus capable of activating expression of genes
115. 2nd messenger for G-protein: cAMP p.12
116. 3rd messenger for G-protein: protein kinase A p. 12
117. 4th messenger for G-protein: gene expression p.12
118. G-protein-linked receptors activate: protein kinase A, this activated enzyme can translocate into the cell nucleus and attach a phosphate group on CREB thereby activating the transcription factor and causing the nearby gene to become activated p.12
119. Ion-channel-linked receptors use: calcium to activate CREB by phosphorylating it. A protein known as calmodulin interacts with calcium and lead to activation of calcium/calmodulin-dependent protein kinase to translocate into the cell nucleus, then add a phosphate group on CREB to activate the transcription factor for gene expression p.12
120. 2nd messenger for ion-channel linked neurotransmission is: calcium p.12 113. in the presence of calcium: calcineurin becomes activated and removes phosphate grops off fourth messenger phosphoprotein p. 15
121. 3rd messenger for ion-channel linked neurotransmission is: calcium/calmodulin-dependent protein kinase (CaMK) p. 12
122. ***third messenger Kinases puts: Phosphates on critical proteins p.16 figure 1-18
123. ***third messenger Phosphatases: undoes what Kinases crease, take phosphates off critical proteins p. 17 , figure 1-19
124. the balance between phosphorylation and dephosphorylation of: 4th-messenger kinases and phosphatases plays a vital role in regulating molecules critical to the chemical neurotransmission process p. 16
125. Hormones such as estrogen, thyroid, and cortisol act at: cytoplasmic receptors, bind them and produce a hormone-nuclear receptor complex that translocates to the cell nucleus, finds elements in the gene that it can influence (called hormone response elements HRE), then acts as a transcription factor to activate nearby genes p.12
126. Neurotrophins trigger their signal transduction pathway by: activating kinase enzyme after kinase enzyme and ultimately changing gene expression p.12 120. Fos and Jun: Transcription factors encoded by EARLY response genes; they turn on late response genes; are also thought of as 5th messenger
127. The neurotrophin cascade pathway is important to know about because it may be responsible for: the expression of genes that regulate synaptogensis and cell survival, and plastic changes that are necessary for learning, memory and disease expression in various brain circuits p.18
128. in summary - first messenger through gene transcription: 1. once 2nd messenger cAMP is fromed from its 1st messenger neurotransmitter, it
129. can interact with a protein kinase 3rd messenger
130. cAMP binds to the inactive or sleeping version of the enzyme and activates protein Kinase,
131. Protein kinase 3rd messenge job is to activate transcription factors by phosphorylating them by sticking a phosphate onto the transcription factor and fom a 4th messenger
132. once a transcription factor is awakened, it binds to genes and cause protein synthesis, an immediate early gene which functions as a 5th messenger
133. when two gene products bind together to form another activated transcription factor, this is the 6th messenger which causes the expression of a late gene product p.21-22
134. Fos and Jun act like a ZIPPER as part of the: 6th messenger and is known as leucine zippers (late gene)
135. epigenetic mechanisms: control how DNA is expressed, can turn off or on p.
136. SERT, NET, EAAT, GAT, GlyT, DAT need to utilize the: sodium pump p.31
137. SERT, NET, DAT, VMAT2 are key targets for most of the: known antidepressants, AND stimulants target DAT, VMAT2 p.51
138. VMAT1, NMAT2, VAChT, VGluT need to utilize the: proton pump - pumps positively charged protons out of the synaptic vesicle so the neurotransmitter can be transported into the synaptic vesicle p.32
139. Sodium Pump Theory: signals resulting from movement of sodium ions into the axon and potassium ions moving out of the axon
140. inactivation of histamine: thought to be entirely enzymatic p.33
141. inactivation of neuropeptides: apparently by diffusion, sequestration and enzymatic destruction p.33
142. SV2A: novel 12-transmembrane synaptic vesicle transporter uncertain mechanism unclear substrates; w/n synaptic vesicle membranes & binds to LEVETIRACETAM
143. Have no known presynaptic transporters: histamine and neuropeptides p.33
144. potently targets several drugs including amphetamine, tetrabenazine, and reserpine: VMATs/SLC18 p. 34
145. Psychotropic drugs target the G-protein-linked receptors: across an agonist spectrum p.35
146. agonist spectrum: no agonist, agonist, partial agonist, antagonist, inverse agonist p.35
147. absence of an agonist, the G-protein-linked receptors are at a very low frequency, referred to as constitutive activity: no agonist p.35
148. producing a conformational change in the G-protein-linked receptor that turns on the synthesis of the second messenger to the greatest effect: agonist p.35-36
149. producing a conformational change in the G-protein-linked receptor that turns on the synthesis of the second messenger to a limited effect: partial agonist p. 37-38
150. blocks the actions of everything, does nothing itself, and will reverse the action of a partial agonist, and reverse an inverse agonist: antagonist p.36 140. binds the receptor to decrease its baseline signal transduction: inverse agonist p.42
151. enzyme activity is the conversion of one molecule into: another molecule p. 44 Figure 2-11
152. irreversible or reversible: binding of enzyme inhibitors to a substrate can be p.42
153. enzyme is unable to bind to its substrate: in the presence of an enzyme inhibitor p.43
154. suicide inhibitors: irreversibly binds to the enzyme protein, permanently inhibiting it and therefore essentially killing it p.44
155. monoamine oxidase (MAO), acetylcholinesterase, and glycogen synthase
156. kinase (GSK): three enzymes that are used in clinical practice p.46
157. promotes cell death (proapoptic action): GSK-3 p.46
158. Lithium: drug that inhibits GSK-3 p.46
159. CYP450 enzymes go through the gut wall, and then sent to the liver to be: biotransformed so the dug can be returned back into the blood stream and then excreted via the the kidney, partially unchanged and partially biotransformed p. 47
160. cyp inhibitors: increase the substrate requiring lower doses p.48
161. cyp inducers: decrease the substrate requiring higher doses p.48
162. 1A2; 2D6; 2C9; 2C19; 3A4: Five of the most important CYP enzymes p.47
163. cigarette smoking induces the: 1A2, thus requiring higher doses of olanzapine, clozapine, zotepine (pines)
164. antidepressant fluvoxamine and antibiotic ciprofloxacin inhibits: 1A2, thus requiring lower doses of clozapine, zotepine, duloxetine or theophylline to reduce side effects and risk of seizures p.48
165. 1A2 substrates: Theophylline, duloxetine, clozapine, olanzapine, zotepine, asenapine, many TCAs, agomelatine p.47-48
166. 5%-10% of Caucasians are poor metabolizers: 2D6 p. 47
167. 2D6 substrates: TCA, thioridazine, codeine, some bb, atomoxetine, venlafaxine, duloxetine, paroxetine, risperidone, clozapine, olanzapine, aripiprazole, iloperidone p.49
168. 2D6 inhibitors: paroxetine, fluoxetine, duloxetine, buproprion, quinidine, ritonavir, asenapine p.49
169. 3A4 substrates: pimozide, alprazolam, triazolam, buspirone, HMG-CoA reductase inhibitors (statins), clozapine, quetiapine, sertindole, aripiprazole, zotepine, lurasidone, iloperidone p.50
170. 3A4 inhibitors: fluvoxamine, fluxetine, negazodone, erythromycin, ketoconazole, protease inhibitors, verapamil, diltiazem p.50
171. 3A4 inducers: Carbamazepine, rifampin, some reverse transcriptase inhibitors (efavirenz, nevirapine), leading to increased metabolism of substrates, thus requiring higher doses of the substrates p.50
172. approximately 20% Asians are poor metabolizers: 2C19 p.47
173. often have elevated levels of the drug in their blood and brains: individuals with low CYP activity p.47
174. Full agonist: Natural neurotransmitters are
1. ligand-gated ion channels, ionotropic receptors, and ion-channel-linked recepters
2. voltage-sensitive or voltage-gated: two major classes of ion channels p.53
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