Drug Modulation of Endogenous Signaling

studied byStudied by 0 people
0.0(0)
learn
LearnA personalized and smart learning plan
exam
Practice TestTake a test on your terms and definitions
spaced repetition
Spaced RepetitionScientifically backed study method
heart puzzle
Matching GameHow quick can you match all your cards?
flashcards
FlashcardsStudy terms and definitions
Get a hint
Hint

5 steps of endogenous chemical signaling

Get a hint
Hint

-synthesis

-release

-distribution

-binding

-removal

Get a hint
Hint

ACh synthesis

Get a hint
Hint

acetyl CoA + choline --> acetylcholine + CoA by choline acetyltransferase (ChAT)

1 / 37

Anonymous user
Anonymous user
encourage image

There's no tags or description

Looks like no one added any tags here yet for you.

38 Terms

1

5 steps of endogenous chemical signaling

-synthesis

-release

-distribution

-binding

-removal

New cards
2

ACh synthesis

acetyl CoA + choline --> acetylcholine + CoA by choline acetyltransferase (ChAT)

New cards
3

ChAT (choline acetyltransferase)

enzyme that synthesizes acetylcholine from acetyl CoA and choline

New cards
4

ACh removal

ACh → choline + acetate by acetylcholinesterase (AChE)

New cards
5

α-NETA

drug that inhibits choline acetyltransferase (ChAT), resulting in reduced ACh synthesis

New cards
6

Botox (botulinum toxin)

toxin that cleaves SNARE proteins to block vesicular release of ACh, resulting in decreased synaptic ACh

New cards
7

neostigmine

drug that inhibits acetylcholinesterase (AChE), preventing ACh degradation resulting in increased ACh signaling

New cards
8

dopamine synthesis

-tyrosine → L-DOPA by tyrosine hydroxylase (TH)

-L-DOPA → DA by DOPA decarboxylase (DDC)

New cards
9

tyrosine hydroxylase (TH)

enzyme that converts tyrosine to L-DOPA

New cards
10

DDC (DOPA decarboxylase)

enzyme that converts L-DOPA into dopamine

New cards
11

dopamine transporter (DAT)

membrane protein on presynaptic cell that reuptakes dopamine from the synapse

New cards
12

AMPT

a drug that inhibits tyrosine hydroxylase (TH), resulting in decreased synthesis of catecholamines such as dopamine

New cards
13

amphetamine

drug that causes vesicular release of DA into cytoplasm, resulting in DA exiting the cell through DAT

New cards
14

cocaine

drug that blocks DAT to prevent DA reuptake from the synapse, resulting in increases DA signaling

New cards
15

CGRP synthesis

encoded in the genome, thus it is expressed and translated into the peptide

New cards
16

peptidases

enzymes that break down proteins, such as CGRP, into peptide fragments

New cards
17

fremanezumab

drug that binds to extracellular CGRP to reduce free peptide available

New cards
18

orthosteric binding site

binding site on a receptor to which the endogenous ligand binds

New cards
19

allosteric binding site

binding site on a receptor that is a different site from where the endogenous ligand binds

New cards
20

orthosteric binding

binding competes with endogenous ligand for the receptor

New cards
21

signaling bias

a measure of the degree to which a drug can selectively activate one signaling pathway over another signaling pathway

New cards
22

example of signaling bias

in MOR signaling, a lower threshold of receptor activation is necessary for recruitment of G-protein signaling versus β-arrestin signaling

New cards
23

allosteric binding

binding to separate site from where orthosteric ligand binds, but affects the receptor's response to orthosteric ligand (affinity or efficacy) either positively or negatively

New cards
24

pure allosteric modulators

allosteric modulators that have no effect on receptor activity on their own

New cards
25

positive allosteric modulator (PAM)

allosteric modulator that increases the net signal by orthosteric ligand by increasing its affinity or efficacy for the receptor

New cards
26

GABAa receptor

ionotropic, pentameric receptor for GABA that allows Cl- ions to enter the cell, thereby inhibiting cell firing; has multiple allosteric sites for benzodiazepines, barbiturates, ethanol, and neurosteroids

New cards
27

GABA binding site

α-β interfaces of GABAa receptor

New cards
28

benzodiazepine binding site

α-γ interfaces of GABAa receptors

New cards
29

benzodiazepines, barbiturates

______ increase frequency of GABAa receptor channel opening in the presence of GABA, while ______ prolong duration of GABAa receptor channel opening in the presence of GABA

New cards
30

negative allosteric modulator (NAM)

allosteric modulator that decreases the net signal by orthosteric ligand by decreasing its affinity or efficacy for the receptor

New cards
31

DMCM

negative allosteric modulator that is a BZ binding site inverse agonist, decreases GABA's action and inhibits BZ action

New cards
32

silent allosteric modulator (SAM)

allosteric modulators that bind to allosteric site on receptor but have no effect on orthosteric ligand's affinity or efficacy; act as allosteric site antagonist

New cards
33

flumazenil

silent allosteric modulator that is an antagonist of the BZ site but has no effect on GABA's action

New cards
34

allosteric agonists

allosteric modulators that have some level of agonist activity on their own

New cards
35

allosteric agonist signaling bias

a biased ability to increase or decrease orthosteric ligand action for different signaling pathways

New cards
36

ago-PAMs and ago-NAMs

positive and negative allosteric modulators that have some level of agonist activity on their own

New cards
37

spatial resolution (allosteric modulators)

allosteric modulators act only where the endogenous ligand is released

New cards
38

temporal resolution (allosteric modulators)

allosteric modulators act only when the endogenous ligand is released

New cards
robot