Pharmacodynamics - part 2

Question 1

What are the 4 generalized physiological actions of xenobiotics?

Answer 1

1) Stimulation of physiological processes (if process is not happening enough)

2) Inhibition of physiological processes (if process is happening too much)

3) Replacement of physiological substances

4) (cyto)Toxic / (cyto)Protective

Question 2

How do most drugs elicit their effects?

Answer 2

By interacting with RECEPTORS (act as receptor ligands).

Some drugs can act directly on DNA, membrane lipids, etc.

Question 3

The protein receptors that drugs can interact with to elicit their effects are referred to as _________ receptors or _________ ___________ receptors.

Answer 3

Regulatory; Signal transduction

Question 4

What are the four main types of receptors?

Which ones are membrane receptors? Which ones are intracellular receptors?

Answer 4

Membrane receptors:
1) Ion channels
2) G-protein linked
3) Tyrosine kinases

Intracellular receptors:
4) Nuclear receptors (ligand activated)

Question 5

Match the following receptors to their brief description:

1) Ion channels
2) G-protein linked
3) Tyrosine kinases
4) Nuclear receptors

A) Agonist binds to the receptor, leading to G-protein activation, which generates a SECOND MESSENGER and activates CELL SIGNALING.

B) Agonist binds to receptor and the complex transports to the nucleus, leading to the ACTIVATION of TRANSCRIPTION and TRANSLATION.

C) Ion (Na+) passes through and leads to the activation of conductance.

D) Agonist binds to the receptor which leads to PHOSPHORYLATION of tyrosines on key signaling molecules, leading to the activation of CELL SIGNALING.

Answer 5

1) Ion channels: Ion (Na+) passes through and leads to the activation of conductance.

2) G-protein linked: Agonist binds to the receptor, leading to G-protein activation, which generates a SECOND MESSENGER and activates CELL SIGNALING.

3) Tyrosine kinases: Agonist binds to the receptor which leads to PHOSPHORYLATION of tyrosines on key signaling molecules, leading to the activation of CELL SIGNALING.

4) Nuclear receptors: Agonist binds to receptor and the complex transports to the nucleus, leading to the ACTIVATION of TRANSCRIPTION and TRANSLATION.

Question 6

(T/F) Ion channels lead to the fastest effect as all the machinery is in place and the nuclear receptors take months to years.

Answer 6

True!

Effects of altered gene expression take time. However, altering gene expression is rapid!

Question 7

Xenobiotics usually _________ bind to receptors to initiate a cellular response.

These bonds are _____. Some of the bonds include _________ bonds and ________ bonds. They are often _____phobic.

Binding is often __________; only one enantiomer forms a three point attachment with the receptor.

Answer 7

REVERSIBLY (allows drug to dissociate from receptor when the drug concentration declines)

Weak; Hydrogen; Ionic; HYDROPHOBIC

Stereospecific.

Question 8

(T/F) Xenobiotics only reversibly bind to the receptors.

Answer 8

False! They can also form permanent covalent bonds with specific receptors.

Question 9

What is affinity?

Answer 9

The tendency of a xenobiotic to bind/combine with its receptor (how easily + long it stays bound).

It is the PRIMARY DETERMINATE of PD potency.

Question 10

What is law of mass of action?

Answer 10

Law of mass of action states that number of receptors occupied by a xenobiotic depends on:
1) Drug concentration
2) Drug receptor ASSOCIATION and DISSOCIATION rate constants (k1 and k2)

Question 11

What is KD?

What does low KD signify? What does high KD signify?

Answer 11

The EQUILIBRIUM DISSOCIATION CONSTANT; K2 (dissociate rate constant) / K1 (association rate constant).

It is the concentration required to saturate 50% of the receptors.

Low KD = greater AFFINITY of the drug for the receptor.

High KD = lower AFFINITY of the drug for the receptor.

Question 12

(T/F) By looking at the KD value we can also determine the efficacy of a drug.

Answer 12

False! KD doesn’t tell us anything about efficacy.

Question 13

What happens if you mix a high KD drug with a low KD drug in a 50:50 ratio?

Answer 13

The high KD does not stay bound for a long time, they get replaced with the low KD.

Low KD outcompetes high KD. It occupies more receptors.

Question 14

Match the following scenarios to their outcomes:

1) Concentration of drug «< KD
2) Concentration of drug&raquo_space;> KD
3) Concentration of drug = KD

A) 100% of receptors occupied (SATURATED)
B) 50% of receptors occupied
C) small number of receptors occupied.

Answer 14

1) Concentration of drug «< KD: small number of receptors occupied.

2) Concentration of drug&raquo_space;> KD: 100% of receptors occupied (SATURATED)

3) Concentration of drug = KD: 50% of receptors occupied

Question 15

(T/F) The amount of drug bound to a receptor can be calculated by [D]/([D] + KD).

[D] = Concentration of drug

Answer 15

True!

Question 16

How can a drug with a high KD (low affinity) achieve the same amounts of receptor bound by a drug with low KD (high affinity)?

Answer 16

Compared to a drug with a low KD (high affinity), a high KD (low affinity) needs MORE drug concentration to occupy the same amounts of receptors.

Question 17

What is efficacy?

Answer 17

The ability of a xenobiotic to initiate a cellular effect.

It is not directly related to receptor affinity.

It varies between molecules that bind to the same receptor.

Question 18

(T/F) Even if a drug’s affinity is really high to a receptor, it can have a low efficacy.

Answer 18

True!

A drug with a lower affinity can have a higher efficacy.

Question 19

An agonist has a _______ intrinsic activity, while an antagonist has a ______ intrinsic activity. A reverse agonist has a ______ intrinsic activity.

All must have ________.

Answer 19

Positive; zero; negative

Affinity

*intrinsic activity = efficacy

Question 20

The greater the occupancy (numbers of receptors occupied by the drug), the ________ the response.

Answer 20

Greater

Question 21

There can be LINEAR and NON-LINEAR RELATIONSHIP between occupancy and response. Briefly describe them.

Answer 21

Linear relationship between occupancy and response: 50% receptor occupancy produces 50% response. One ligand binds to one receptor and produces 1 unit of response. 1:1 ratio.

Non-linear relationship between occupancy and response: 5% receptor occupancy produces 50% response. One ligand binds to one receptor and produces 50000 units of response (can activate multiple proteins). 1:2/3/4… ratio.

Question 22

What are the different types of agonists, antagonists and allosteric modulators (ligands)?

Answer 22

Agonists: full, partial, and inverse

Antagonists: competitive, non-competitive

Allosteric modulators: positive, negative

Question 23

Agonists bind/occupy receptors and lead to a _________ ______ and receptor _________.

Antagonists bind/occupy receptors and produce NO __________ ________ or a change that does NOT lead to receptor __________.

Answer 23

Conformational change; activation

Question 24

(T/F) Usually an agonist drug has a higher efficacy than the endogenous molecule.

Answer 24

True!

Question 25

Match the following agonists to their definitions:

1) Full agonist
2) Partial agonist
3) Inverse agonist

A) Decreases the rate of basal signal transduction that occurs in the absence of a ligand.

B) Produce the MAXIMAL RESPONSE obtainable in a tissue; MAXIMAL EFFICACY. (occupies 100% of the receptors)

C) Produce a SUBMAXIMAL RESPONSE. (occupies 1-99% of the receptors)

Answer 25

Full agonist: Produce the MAXIMAL RESPONSE obtainable in a tissue; MAXIMAL EFFICACY. (occupies 100% of the receptors; 100% of response)

2) Partial agonist: Produce a SUBMAXIMAL RESPONSE. (occupies 1-99% of the receptors; 1-99% of response)

3) Inverse agonist: Decreases the rate of basal signal transduction that occurs in the absence of a ligand.

Question 26

(T/F) Agonists are more potent (ED50) than antagonists.

Answer 26

True! Less dose of the agonist required to reach 50% of the maximal effect.

Question 27

Partial agonists can act as antagonists when with a full agonist.

Match the scenarios with their outcomes:

1) Partial agonists with LOW EFFICACY
2) Partial agonists with MODERATE EFFICACY
3) Partial agonists with HIGH EFFICACY

A) partial agonists almost always act as agonists.
B) acts as an antagonist by reducing full agonist binding and receptor activation.
C) partial agonists act as agonists with low-moderate basal activity but as antagonists with high basal activity or in the presence of exogenous agonist.

Answer 27

Partial agonists with LOW EFFICACY: acts as an antagonist by reducing full agonist binding and receptor activation.

Partial agonists with MODERATE EFFICACY: partial agonists act as agonists with low-moderate basal activity but as antagonists with high basal activity or in the presence of exogenous agonist.

Partial agonists with HIGH EFFICACY: partial agonists almost always act as agonists.

Question 28

Describe how a partial agonist can act as an antagonist in the presence of a full agonist (the receptor’s endogenous molecule).

Answer 28

If it is a full agonist, it would generate 10 units of response if 10 of them bind to the receptor.

But when a partial agonist comes along (same affinity) in a 50:50 ratio with the agonist, 5 of it bind to the receptor.

If it generates 0.1 unit of response for one bound receptor, now there is a total of 5.5 units of response instead of 10!

Question 29

Some receptors have multiple binding sites for which different ligands hold different _______ and different _________ activity.

Xenobiotics and endogenous ligands may bind common or distinct sites. Binding at one site causes ___________ change, influencing _________ & _________ at other sites.

Answer 29

Affinity; Intrinsic

Conformational; binding; activation

Question 30

What are co-agonists?

Answer 30

Sometimes multiple agonists are needed to activate a receptor.

Co-agonists work together with other co-agonists to activate target receptors.

Question 31

(T/F) In an ion channel, an UNCOMPETITIVE antagonist would block the channel itself.

Answer 31

True!

Question 32

Allosteric modulators bind receptors at ___________ sites. They have no ________ when bound to a receptor alone.

Answer 32

Allosteric (different site than of agonists)

Efficacy (intrinsic activity)

Question 33

What can allosteric modulators affect?

Answer 33

1) They can increase or decrease the affinity of a receptor + ligand (agonist) complex.

2) They can increase or decrease the efficacy of the agonist.

3) They can slow or accelerate receptor up- or down-regulation.

Question 34

Match the functions of these ligands to their functions when alone:

1) Full agonist
2) Partial agonist
3) Inverse agonist
4) Competitive antagonist
5) Non-competitive antagonist
6) Positive allosteric modulator
7 Negative allosteric modulator

A) Inverse agonism
B) Agonism
C) None

Answer 34

1) Full agonist: Agonism

2) Partial agonist: Agonism

3) Inverse agonist: Inverse agonism (antagonistically reduces endogenous tone)

4) Competitive antagonist: None

5) Non-competitive antagonist: None

6) Positive allosteric modulator: None

7 Negative allosteric modulator: None

Question 35

Match the functions of these ligands to their functions with a FULL AGONIST PRESENT:

1) Full agonist
2) Partial agonist
3) Inverse agonist
4) Competitive antagonist
5) Non-competitive antagonist
6) Positive allosteric modulator
7) Negative allosteric modulator

A) Synergism/potentiation
B) Antagonism
C) Agonism

Answer 35

1) Full agonist: agonism

2) Partial agonist: antagonism

3) Inverse agonist: antagonism

4) Competitive antagonist: antagonism

5) Non-competitive antagonist: antagonism

6) Positive allosteric modulator: Synergism/potentiation

7) Negative allosteric modulator: antagonism

Question 36

(T/F) Xenobiotic mixtures are usually composed of similar compounds with common receptors and binding sites.

Answer 36

False! Xenobiotic mixtures can be composed of similar OR DISSIMILAR compounds with common OR DISTINCT receptors + binding sites.

Question 37

What are the four interactive effects of xenobiotic mixtures? Briefly describe them.

Answer 37

1) Additive (summation): when the effect of two drugs given in combination equals the mathematical summation of their effects when given alone.

2) Synergistic: when the combine effect of two drugs is greater than the sum of their effects when given separately.

3) Antagonistic: when the effect of two drugs is less than either of their effects when given alone.

4) Indifferent (masked): no change

*these effects can occur at all levels; molecular, cellular, systemic.

Question 38

A _________ allosteric modulator can lead to synergism and a __________ allosteric modulator can lead to antagonism.

Answer 38

Positive; negative

Question 39

What is potentiation?

Answer 39

It is a type of synergism; when one drug does not elicit a response on its own but enhances the response to another drug through an indirect/allosteric effect.

Question 40

(T/F) Potentiation is driven by pharmacokinetics and pharmacodynamics. If B (a positive allosteric modulator) impacts bioavailability (PK) of Prodrug A, it can generate a higher response (PD).

Answer 40

True!

Question 41

What is the difference between specificity and selectivity?

Answer 41

Specificity - relates to the number of different mechanisms involved in xenobiotic/endogenous ligand action (how many receptors can it activate)

Selectivity - the preference of the drug to one receptor (as compared to other receptors). It is the ability of the drug to produce one pharmacological effect over others. If a drug is selective, it will preferably bind to one receptor, but it can bind to others by increasing its concentration.

Question 42

Xenobiotics with a ______ specificity act on single targets, while xenobiotics with a ________ specificity act through multiple mechanisms of action.

Answer 42

High; low/none

Eg. salbutamol only acts on b2-adrenoceptor, while phenothiazine acts on D2-dopamine, alpha-adrenergic, and muscarinic receptors.

Question 43

(T/F) Most drugs are specific rather than selective.

Answer 43

False! Most drugs are selective rather than specific.

Question 44

Selectivity is enhanced by increasing __________ for target receptors.

Answer 44

Affinity

Question 45

(T/F) For drugs with a low specificity (can act on multiple receptors), as the concentration of the drug increases, other receptors with low selectivity can be activated, leading to side effects.

Answer 45

True!

Question 46

What is the difference between down regulation and up regulation? Give examples of both.

Answer 46

Down regulation: continued exposure of a receptor to an agonist leads to a DECREASED response to the agonist. Receptors are reduced and decreases the cell’s sensitivity to an agonist or drug. Ex. asthma patients treated continuously with salbutamol have their B2-adrenoceptor down-regulated.

Up regulation: prolonged deprivation of the agonist or prolonged exposure to antagonists result in SUPERSENSITIVITY of the receptor.

For example, administration of beta-blockers (antagonist) upregulates β adrenoreceptors. Thus, if β-blockers are abruptly stopped, it can cause rebound hypertension because of the sudden stimulation of a large number of β adrenoreceptors.

Question 47

What are the two down regulation mechanisms?

Answer 47

1) Masking/internalization (removal) of the receptor
2) Decreased synthesis or increased degradation of the receptor

Question 48

What are the two up regulation mechanisms?

Answer 48

1) Unmasking of the receptor
2) Increased synthesis or decreased degradation of the receptor

Question 49

What are ionotropic receptors? Give 4 examples.

Answer 49

Ionotropic receptors are membrane-bound ligand gated ion channels.

Calcium channels
Nicotinic acetylcholine receptor
GABA receptor
NMDA receptor

Question 50

Where are ionotropics receptors found?

Answer 50

They are found at NEUROMUSCULAR JUNCTIONS and POSTSYNAPTIC MEMBRANES.

Question 51

Fill in the blanks regarding membrane excitability:

Relative to extracellular space, the inner nerve/muscle membrane maintains a charge of ________.

Influx of positive ions _____________ the cell and establishes an ___________ _________ which is propagated down the neuron by VOLTAGE dependent _____ channels.

At neuromuscular junctions, the action potential activates INTRACELLULAR ______ channels resulting in muscle ___________.

Efflux of _______ ions or influx of _______ ions repolazies.

Answer 51

-70mV

Depolarizes; action potential; Na+

Calcium; CONTRACTION

Positive; Negative

Question 52

How are the different calcium channels classified?

Answer 52

They are classified based on their:
1) Mechanisms of actions
2) Ligands
3) Physiological roles
4) Inhibition by different toxins

Different calcium channels are found in different tissues and cell types.

Question 53

(T/F) All calcium channels are transmembrane and allow the passage of calcium channels.

Answer 53

True!

Question 54

(T/F) Different ligands can bind at the same/different receptor sites to activate/block the same receptor. The same ligand may have similar/different affinity for different receptor sub-types.

Answer 54

True!

Question 55

What is CROSS-TALK?

Answer 55

Cross talk can occur with receptors or signaling pathways.

Receptor cross-talk refers to the up or down regulation of receptors or their actions via the actions of heterologous receptors and their signaling intermediates.

Similarly, there can be cross talk with signaling pathways (components are shared between two or more signaling pathways or components of one pathway are modified directly by enzymes acting in other signaling pathways).

Question 56

Acetylcholine receptors are another form of ion channels. These regulate the balance between excitation and inhibition in muscles.

Its agonists are ___________ (endogenous ligand) and _________.

Its antagonists are __________ (irreversible) and ______ (reversible).

Nicotinic acetylcholine receptor antagonists lead to _____ _____________.

Nicotinic acetylcholine receptor agonists lead to receptor ____________ and muscle ____________.

Answer 56

Acetylcholine; nicotine

Imidacloprid; curare

Low movements

Activation; CONTRACTION

Question 57

(T/F) Nicotine over-activates signaling in insects; toxicity varies between taxa.

Answer 57

True!

Question 58

Briefly answer the questions regarding GABA receptors:

1) What are GABA receptors?

2) Where are they found?

3) What kind of message do they relay?

Answer 58

1) GABA receptors are ligand-gated chloride channels that remove polarization of positive ions. They are permeable to Cl- ions.

2) They are found at POST-SYNAPTIC MEMBRANE OF GABA-ergic synapses

3) Inhibitory message (prevents firing of new action potential)

Question 59

Briefly answer the questions regarding NMDA receptors:

1) What are NMDA receptors?

2) Where are they located?

3) What kind of message do they relay?

Answer 59

1) NMDA receptros are ligand-gated cation channels activated by an excitatory neurotransmitter, glutamate. They are permeable to K+ and Ca2+ ions.

2) They are located at post-synaptic density region of excitatory synapses.

3) Excitatory message

Question 60

For most ionotropic receptors, channel __________ is the same for different agonists (rate of ion flow).

Agonists differ in channel _________ they induce.

Answer 60

conductance

lifetime (how long they stay open)

Question 61

What is the Opening constant of a ionotrpoic receptor?

What is the Closing constant of an ionotropic receptor?

Answer 61

Opening constant: Beta β

Closing constant: Alpha α

Question 62

Match the ligands of ionotropic receptors to their definitions:

1) High efficacy agonist
2) Low efficacy agonist
3) Antagonist

A) Ion is closed; β = 0

B) Activates a large proportion of a receptors at a time (more open at a longer time); β > α

C) Activates fewer receptors at a time; α > β

Answer 62

High efficacy agonist: activates a large proportion of a receptors at a time (more open at a longer time) β > α

Low efficacy agonist: activates fewer receptors at a time; α > β

Antagonist: ion is closed; β = 0 (no opening constant)

Question 63

G-protein coupled receptor family (GPCRs) is also referred to as ___________ receptors.

Answer 63

Metabotropic

Question 64

What are some examples of GPCRs?

Answer 64

Acetylcholine (muscarinic), Adrenaline (adrenergic), Serotonin, Opiates and Dopamine.

Question 65

While the nicotinic acetylcholine is a ________ protein and the muscarinic acetylcholine is a __________.

Answer 65

Channel; GPCRs

Question 66

Describe the basic structure of the G-protein coupled receptors. Mention which parts are strongly conserved and which ones are less conserved.

Answer 66

They are usually 400-500 AMINO ACIDS in length.

They have SEVEN TRANSMEMBRANE SEGMENTS; sometimes called “serpentine receptors”

The helices are strongly conserved.

The extracellular amino terminus and the intracellular carboxyl termini vary in length and sequence are less well conserved.

Question 67

What happens when a ligand binds to a G-protein coupled receptor?

Answer 67

When a ligand binds to the GPCR in the extracellular side, HETEROMERIC G-proteins (α,β,γ) are recruited.

This activates the G-protein as the GDP —> GTP, leading to the activation of an effector molecule (second messenger).

Question 68

Different G proteins activate different effectors. While Gαs __________ adenylate cyclase, Gαi _________ adenylate cyclase.

Answer 68

Stimulates; inactivates.

Some inhibitory and stimulatory receptors have the same target EFFECTORS.

Question 69

Match the two main groups of Adrenergic GPCRs to their definitions:

1) α Adrenergic receptors
2) β Adrenergic receptors

A) have the subtypes β1, β2, β3 which are all linked G proteins which in turn are linked to adenylate cyclase

B) have subtypes α1 and α2

Answer 69

α Adrenergic receptors: have subtypes α1 and α2

β Adrenergic receptors: have the subtypes β1, β2, β3 which are all linked G proteins which in turn are linked to adenylate cyclase

Ligands have different degrees of selectivity for these subtypes. If you want to treat lungs using β1, β2 receptors that work both on heart + lungs, you have to find molecules with high selectivity for the receptors in lungs and less for heart.

Question 70

What are the functions of dopamine pathways?

What are the functions of serotonin pathways?

Answer 70

Dopamine pathways: reward, pleasure, euphoria, motor function, compulsion, preservation

Serotonin pathway: mood, memory processing, sleep, cognition

Question 71

If there are fewer receptors, you need a ________ dose for the same effects.

Answer 71

Larger

Question 72

Receptor tyrosine kinases are also known as _____________-________ receptors or ________________ receptors.

Answer 72

Enzyme-linked; autophosphorylating

Question 73

What are the five classes of receptor tyrosine kinases?

Answer 73

1) Epidermal growth factor (EGF-R) receptor family
2) Insulin receptor
3) Platelet-derived growth factor (PDGF)
4) Fibroblast growth factor (FGF)
5) Vascular endothelial growth factor (VEGF)

Question 74

Upon _________ (a result of ligands being bound to both receptors), tyrosine kinases catalyze their own phosphorylation.

They can also ______________ other proteins when activated.

Answer 74

Dimerization

Transphosphorylate

Question 75

Grb2 is an adaptor protein containing SH2 and SH3 domains.

What is the function of SH2?

What is the function of SH3?

Answer 75

The Src homology 2 (SH2) domain is implicated in a number of signal transduction pathways. Its primary function is to bind PHOSPHOTYROSINES on the tyrosine kinase receptors, which localizes different proteins necessary to transmit the proper function.

The Src homology 3 (SH3) domain mediates protein-protein interactions by binding to PROLINE-RICH regions of other proteins.

*SH2 bind to receptor tyrosine kinases after they dimerize and phosphorylate

Question 76

(T/F) Growth factors lead to activation of genes involved in cell proliferation, cell survival and angiogenesis.

Answer 76

True!

Question 77

Many cancer cells have either increased numbers of __________ _________ receptors or they have acquired a mutation to make them constantly _______.

Answer 77

Tyrosine Kinase Receptors

Active

Thus, inhibitors of these receptors are often used in cancer therapeutics!

Question 78

What are nuclear receptors?

Answer 78

Nuclear receptors are a family of ligand-regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various other lipid-soluble signals, including retinoic acid and thyroid hormone.

Question 79

What class out of the five classes of receptor tyrosine kinases has a rapid response?

Answer 79

Insulin receptor! Others are all growth factors that affect transcription, which leads to slow response.

Insulin receptor does not involve transcription of genes. Its machinery is already in place!

Question 80

What are the two main groups of nuclear receptors? Give examples of both.

Answer 80

1) Steroid receptors: glucocorticoid, mineralocorticoid, progesterone, androgen + estrogen

2) Others: Thyroid hormone receptor 3, Retinoic acid receptors, Vitamin D3 receptors, Peroxisome proliferator activated receptors (PPARs).

Question 81

Nuclear receptors are composed of a N-terminal domain, DNA binding domain, hinge region, ligand binding domain and a C-terminal domain.

Which ones are highly/moderately conserved?

Answer 81

DNA binding domain is highly conserved.

Ligand binding domain is moderately conserved.

Lots of variability in the N/C-terminal domain.

Question 82

Nuclear receptors regulate gene transcription.

How do nuclear receptors activate specific genes?

Answer 82

They recognize specific sequences of DNA called Hormone Response Elements (HREs) which are a class of promoter enhancers.

These HREs occur as repeated and/or inverted sequences.

There are two identical/similar parts to the HRE called “half-site motifs” that each bind to a nuclear receptor.

Nuclear receptors bind DNA as monomers/dimers.

Question 83

What is the difference between Type I and Type II nuclear receptors?

Answer 83

Type I: Receptors located in the cytoplasm of a cell. These receptors are translocated to the nucleus after stimulation by an agonist. Steroid receptors.

Type II: Receptors located in the nucleus of a cell, even in the absence of agonists. Others (vitamin D3, thyroid, etc)

Question 84

Briefly describe the differences between Type I and Type II nuclear receptors activation.

Answer 84

Type I: In absence of a ligand, receptor is inhibited by being bound to a chaperone in the cytoplasm. Once a ligand comes and binds to the receptor, it dissociates from the chaperone and dimerizes (homodimers) and goes to the nucleus to bind to the response element of a gene, activating gene transcription.

Type II: Receptor is already bound to the response element with another receptor RXR (heterodimers) in the response element of a gene. It is inhibited by a corepressor. Once ligand binds to it, coactivator replaces corepressor and gene transcription is activated.

Question 85

(T/F) In heterodimeric nuclear receptors, co-repressor complex keeps the gene silent when there is no ligand around.

Answer 85

True!

*Heterodimeric nuclear receptor = Non-steroid receptors = Type II receptors.

Question 86

What is the Zn finger? What are its P box and D box?

Answer 86

Zn finger functions in DNA binding of nuclear receptors to activate specific genes. It has a P and a D box.

The P (proximal) box is a primary nucleotide sequence, which is shared among most nuclear receptors.

The D (distal) box is a spacing of the half-site motif. These sequences are different in all nuclear receptors.

Question 87

Estrogen receptors are nuclear receptors that are expressed in the:

Answer 87

Cytoplasm, cell membrane, nucleus, and intracellular membranes.

They have sub-type and cell-specific effects.

Question 88

(T/F) Estrogen promote formation of fallopian tubes, uterus, and female secondary sexual characteristics. They play an essential role in menstrual cycle/ovulation in follicular and luteal phase.

Answer 88

True!

Question 89

(T/F) A ligand can be an agonist at one receptor but an antagonist at a different receptor.

Answer 89

True!

Question 90

What is Mannitol?

Answer 90

Mannitol is a drug that makes use of one of the three methods (PHYSICAL ACTION) a xenobiotic can make use to induce a change in the organism.

Mannitol is a diuretic used to force urine production in people with kidney failure. It reduces water levels inside the system. The high concentration in the GI tract causes water to go in there, increasing urination.

Question 91

What are antacids?

Answer 91

Antacids are drugs that makes use of one of the three methods (CHEMICAL ACTION) a xenobiotic can make use to induce a change in the organism.

They add base to stomach, reducing hydrogen ions.

Question 92

What are antioxidants?

Answer 92

Antioxidants are drugs that makes use of one of the three methods (CHEMICAL ACTION) a xenobiotic can make use to induce a change in the organism.

When a stable molecule is oxidized, it leads to a free radical leading to a chain reaction where the radical can react with fatty acid in the membrane (aka lipid peroxidation). This leads to development of different diseases.

Antioxidants stabilize the free radicals, preventing the chain reaction.

Question 93

_________ pro-oxidants, _______ anti-oxidants leads to the production of free radicals, leading to lipid/protein/DNA pre/oxidation.

Answer 93

Increased; Decreased