Exam 2 Review, Neuropharmacology

Front 1

Converts glutamate into GABA

Back 1

GAD (glutamic acid decarboxylase

Front 2

De novo synthesis pathway for Catecholamines

Back 2

tyrosine-->(tyrosine hydroxylase)-->DOPA(AADC)--> Dopamine--->(dopamin beta hydroxylase)---> Norepinephrine

Front 3

Synthesis inhibitor of TH

Back 3

AMPT

Front 4

Catecholamine breakdown enzymes

Back 4

MAO (Monoamine-oxidase) and COMT (Catechol-O-Methyltransferase)

Front 5

Dopaminergic pathways

Back 5

Project from Substantia Nigra, Ventral Tegmental Area.
Large populations of DA receiving neurons in the Basal Ganglia and the Nucleus Accumbens

Front 6

Dopamine receptor subtypes

Back 6

D1 and D2 Classes

Front 7

D1 class

Back 7

includes: D1 and D5 subtypes
generally excitatory
coupled to GalphaS proteins
Direct facilitation of NMDA Glutamate receptors, probably through Beta subunits
Indirect facilitation of AMPA glutamate receptors
inhibition of protein phosphetase activity

Front 8

D2 class

Back 8

D2, D3, D4 subtypes
generally inhibitory
direct facilitation of potassium channels through Beta subunit of GalphaI protein
indirect facilitation of AMPA glutamate receptors.

Front 9

Locus Coeruleus

Back 9

A system in which alterations of a very small number of neurons can be broadcast to a vast number of brain regions and neuronal populations to have widespread effects

Front 10

NE receptors

Back 10

Alpha and beta families

Front 11

NE alpha 1 receptors

Back 11

Coupled to GalphaQ proteins
slowly depolarizes neuronal membrane
inhibits 2 pore domain potassium channels
increases cellular excitability

Front 12

NE alpha 2 receptors

Back 12

coupled to GalphaI proteins
primary autoreceptor for NE signaling
decreases cellular excitability
blocks Ca++ channels

Front 13

NE autoreceptor

Back 13

Alpha 2
decreases firing rate
hyperpolarization (inhibits Ca++ channels)
decreases synthesis and release of NE

Front 14

serotonin

Back 14

monoamine; indolamine
Found in serum, has effects on vascular muscle tone
90% found in the gut

Front 15

serotonin synthesis pathway

Back 15

L-tryptophan---> (tryptophan hydroxylase)--->L-5-hydroxytryptophan---> (Aromatic Amino Acid decarboxylase)--->serotonin

Front 16

Serotonin regulation

Back 16

Substrate availability is a limiting factor, Tryptophan is an essential amino acid and must be supplied through the diet

Tryptophan hydroxylase is governed by the level of firing of serotonin neurons. Electrical stimulation increases activity of TH. In state of Hyperpolarization, activity is dependent on CamKII phosphorylization.

Front 17

Serotonin Release transporter

Back 17

Vesicular Monoamine Transporter (VMAT)
Same as Catecholamines

Front 18

Serotonin Reuptake

Back 18

Serotonin Reuptake Transporter (SERT)

Front 19

Serotonin Reuptake Inhibitor

Back 19

Reserpine (SERT blocker)

Front 20

Serotonin Pools

Back 20

Readily available ~ 25%
reserve pool ~ 75%

Front 21

Fenfluramine

Back 21

Appetite suppressant , has the effect of increasing serotonin release through reversal of SERT (very similar to the effects of amphetamine on DAT)

Front 22

Serotonergic Anatomy

Back 22

Dorsal raphe (caudal), Median Raphe (caudal), Dorsal raphe (rostral)

Front 23

Serotonin release systems

Back 23

Fibers, Varicosities are release sites

Front 24

Serotonin D system

Back 24

Dorsal raphe, Thin spindles with varicose release sites

Front 25

Serotonin M system

Back 25

Medial raphe, thick non varicose tracts

Front 26

5HT1

Back 26

Serotonin autoreceptor, Metabotropic, direct interaction with potassium channels

Front 27

5HT2

Back 27

metabotropic, Excitatory, LSD has high affinity for this receptor

Front 28

5HT3

Back 28

Ionotropic, ligand gated sodium channel, heteropentameric structure of subunits.

Front 29

acetylcholine breakdown enzyme

Back 29

acetylcholinesterase

Front 30

Nicotinic receptors

Back 30

Ionotropic, permeable to Ca++ and Na+
comprised of 5 subunits, many different isoforms

Front 31

muscarinic receptors

Back 31

metabotropic, coupled to GalphaI or GalphaQ protein complexes.

Front 32

neuropeptides

Back 32

small proteins that act as neurotransmitters, but have wider variation in function. Can be released directly into the blood stream and act as hormones.
Act on peripheral organs

Front 33

neuropeptide synthesis

Back 33

coded for by mrna, synthesized at the ER, undergo alternative splicing to produce wide many different funtional neuropeptides.
mRNA---> prepropeptide---->propeptide---->enzymatic modification

Front 34

neuropeptide release

Back 34

frequency dependent. Burst firing or increased action potentials leading to prolonged Ca++ required for release. Neuropeptides are costly energy wise, and therefore have very important functions.

Front 35

Mu opioid receptor

Back 35

metabotropic, binds to beta-endorphin

Front 36

delta opioid receptor

Back 36

metabotropic, binds to beta enkephalin

Front 37

Kappa opioid receptor

Back 37

binds to dynorphin (produces dysphoria)

Front 38

neuropeptide receptor localization

Back 38

determines functionial characteristics

Front 39

orexin effects

Back 39

stimulates wakefulness, stimulates hunger

Front 40

oxytocin

Back 40

important for pair bonding, labor induction, "the love hormone"