Unit 2: ANS Cell Communication

Question 1

most common control system (feedback loop) for maintaining homeostasis

Answer 1

negative feedback loop

Question 2

example of endocrine cell signaling

Answer 2

adrenal medulla releases epinephrine that binds to B1 receptors on heart

Question 3

example of autocrine cell signaling

Answer 3

NE binding to presynaptic A2 receptor on same nerve terminal that released NE.

Question 4

neurotransmitter signaling is a specific type of which form of cellular communication?

Answer 4

paracrine signaling

Question 5

example of a receptor that performs compartmentalization

Answer 5

ryanodine receptor (Ryr) is a scaffolding protein. multiple components of signaling pathways come together on scaffolding proteins to increase their concentrations and effects
calcium channels do this as well

Question 6

general flow through GPCR

Answer 6

first messenger (ligand) –> receptor –> effector –> second messenger –> cellular response

Question 7

name 3 chemical messengers derived from arachidonic acid (these are all lipophilic)

Answer 7

prostaglandins
leukotrienes
thromboxanes (eicosanoids. ex: anandamide)

Question 8

chemical messengers derived from tyrosine (4)

Answer 8

dopamine
NE
epi
iodothyronines

Question 9

characteristics of steroid chemical messengers
derived from:
where they bind on target cells:
storage:
how they circulate in the blood:

Answer 9

derived from cholesterol
circulate in blood bound to a protein
bind to receptors in cytoplasm or nucleus of target cells
not stored in producing cells

Question 10

characteristics of eicosanoid chemical messengers
derived from
primarily what kind of actions
how they bind to the cell
storage
precursor

Answer 10

derived from polyunsaturated fatty acids
arachidonic acid is main precursor
primarily autocrine and paracrine actions
unlike steroids, they usually bind to cell surface receptors
not stored in producing cells

Question 11

which category of signaling molecules are stored in vesicles in the cells that synthesize the molecule (2)

Answer 11

hydrophilic messengers
peptide and protein messengers

Question 12

endogenous opioid peptides include (6)

Answer 12

beta endorphins
dynorphins
enkephalins
substance P
calcitonin gene related peptide (CGRP)
orexins

Question 13

hydrophilic chemical messengers include (4)

Answer 13

amino acids (glycine, glutamate, gaba, aspartate)
biogenic amines (DA, NE, epi, serotonin, histamine)
choline esters (Ach)
iodothyroxines (T4, T3)

Question 14

lipophilic chemical messengers include 2 categories (2 examples)

Answer 14

steroids (aldosterone, cortisol, testosterone, progesterone, estrogens)
eicosanoids (prostaglandins, leukotrienes, thromboxanes)
VitD, retinoids

Question 15

how to G proteins turn off

Answer 15

GTPase activity in alpha subunit. catalyzes hydrolysis of GTP to GDP and Pi.
alpha subunit dissociates with effector and goes back to beta-gamma subunit

Question 16

what is bound to the alpha subunit of a GPCR when its in the off/inactive state

Answer 16

GDP

Question 17

what is bound to the alpha subunit of a GPCR when a ligand has attached to the GPCR and it is turned “on” or in the active state

Answer 17

GTP

Question 18

in the GPCR, what does the GDP GTP exchange do to the aby complex (after activation)

Answer 18

aby complex disassembles into GTP bound alpha subunit and separate beta-gamma complex

Question 19

in the activated GPCR, the alpha GTP subunit will interact with effectors that include (3)

Answer 19

adenylate cyclases (AC)
phospholipase C (PLC)
phospholipase A2 (PLA2)

Question 20

in the activated GPCR, the beta-gamma complex subunit will interact with effectors that include either

Answer 20

Gi-0 regulated potassium channels (GIRK)
VgCa2+ channels
B adrenergic receptor kinase (BARK)

Question 21

heterotrimeric G proteins are classified into 4 families based on nature of alpha subunit (and what they stimulate/inhibit)

Answer 21

Gs (stimulates adenylate cyclase)
Gi, 0 (inhibits adenylate cyclase)
Gq, 11 (activates PLC)
G12, 13 (activates small G proteins)

Question 22

activated GPCR alpha subunits target these 3 big down stream effectors (and know their second messengers)

Answer 22

adenylyl cyclase (AC) –> cyclic adenosine monophosphatate (cAMP)
phospholipase C (PLC) –> inositol triphosphate (IT3) and diacylglycerol (DAG)
phospholipase A2 (PLC2) –> eicosanoids (20 carbon lipid mediators)

remember eicosanoids are derived from arachadonic acid

Question 23

adenylyl cyclase function, inbhibition and stimulation

Answer 23

AC converts ATP to cAMP
Gs stimulates cAMP while Gi inhibits cAMP

Question 24

PLC function and stimulation

Answer 24

PLC converts PIP2 to IP3 and DAG (both second messengers)
Gq11 with Ca2+ activates PLC

Question 25

function of IP3

Answer 25

soluble, diffuses into cytoplasm, binds to Ca2+ channels on ER. Ca2+ then is released into cytoplasm from ER

Question 26

function of DAG

Answer 26

acts as docking site for activator PKC

Question 27

function of increased cAMP in: cardiac myocyte AW and vessel smooth muscle platelets principal cell of nephron

Answer 27

cardiac myocyte: increased cAMP increases contractility via b1 receptors AW and vessel smooth muscle: b2- increased cAMP causes relaxation and dilation platelets: increased cAMP decreases aggregation (adenosine, P1A2 receptor) principal cell of nephron: v2- increased cAMP promotes insertion of aquaporin 2 channels in apical membrane

Question 28

how is the action of cAMP terminated

Answer 28

phosphodiasterases

Question 29

how is the action of DAG terminated

Answer 29

when the molecule is recycled into new phospholipids

Question 30

how is the action of IP3 terminated

Answer 30

when the molecule is recycled into new phospholipids

Question 31

why is free Ca2+ a second messenger

Answer 31

because its an intracellular messenger

Question 32

which two calcium transporters are found in the plasma membrane

Answer 32

sodium calcium exchanger (NCX) Ca2+ ATPase (Pump, PMCA)

Question 33

two types of human synapses in the body

Answer 33

chemical and electrical

Question 34

Ach synthesis (6 steps)

Answer 34

1. glucose enters nerve terminal by facilitated diffusion 2. glycolysis converts glucose to pyruvate 3. pyruvate is transported into mitochondrion. acetyl group from pyruvate is added to coenzyme A tp produce acetyl co-A which is transported back into the cytoplasm 4. choline is actively transported into presynaptic terminal. choline is rate limiting step in Ach synthesis 5. choline acetyltransferase (CHAT) catalayzes formation of Ach from acetyl CoA and choline 6. Ach is transported into vesicles by H+ anti porter. ach is stored in synaptic vesicles until release

Question 35

explain Ach elimination

Answer 35

acetylcholinesterase (AchE) in the synaptic cleft hydrolyzes Ach to acetate and choline. choline re enters the nerve terminal and is re used for Ach synthesis

Question 36

what is required to initiate conformational change for nAchR's

Answer 36

binding of two Ach's to the alpha subunits

Question 37

where are MAchR's found (4)

Answer 37

CNS, heart, smooth muscle, glands of Gi tract

Question 38

Gq MAchR's include

Answer 38

M1, M3, M5 (all have same second messenger pathway)

Question 39

Gi MAchR's include

Answer 39

M2, M4

Question 40

Receptor: NmAchR's Signal Transduction: Locations: Responses:

Answer 40

Signal Transduction: opening of nonselective cation channels, influx of Na Locations: skeletal muscle at NMJ Responses: end plate depol and skeletal muscle contraction

Question 41

Receptor: NnAchR's Signal Transduction: Locations: (3) Responses: (5)

Answer 41

Signal Transduction: opening of nonselective cation channels, influx of Na Locations: autonomic ganglia, adrenal medulla, CNS Responses: depol of postsynaptic postganglionic neuron, secretion of catecholamines, arousal, attention, analgesia

Question 42

Receptor: M1 Signal Transduction: Locations: (2) Responses: (4)

Answer 42

Signal Transduction: Gq11 --> PLC --> IP3 --> increase in DAG --> increase in Ca2+ --> increase in PKC Locations: autonomic ganglia, CNS Responses: excitatory response, arousal, attention, analgesia

Question 43

Receptor: M2 Signal Transduction: Locations: (2 specific) Responses: (3)

Answer 43

Signal Transduction: by subunit of Gi--> increase in K (GIRK) opening Locations: heart: nodal tissue and cardiac muscle Responses: slowed spontaneous depolarization (decreased chronotropy, inotropy, dromotropy)

Question 44

Receptor: M3 Signal Transduction: Locations: (2) Responses: (2)

Answer 44

Signal Transduction: Gq11 --> PLC --> increase in IP3 --> increase in DAG -->increase in Ca2+ and PKC Locations: smooth muscle and Gi Responses: contraction and increase in salivary secretions

Question 45

Receptor: M4 Signal Transduction: Locations: (1) Responses: (1)

Answer 45

Signal Transduction: Gi, 0 --> inhibits AC -->decrease in cAMP --> By subunit of Gi--> increase in GIRK (K channel) opening Locations: CNS Responses: negative feedback to decrease Ach release

Question 46

Receptor: M5 Signal Transduction: Locations: (1) Responses: (2)

Answer 46

Signal Transduction: Gq11 --> PLC --> IP3 -->increase in DAG -->Ca2+ --> and PKC Locations: CNS Responses: promotes dopamine release, dilation of cerebral arteries

Question 47

primary excitatory neurotransmitter in the brain

Answer 47

glutamate

Question 48

primary inhibitory neurotransmitter in the brain

Answer 48

GABA

Question 49

primary inhibitory neurotransmitter in spinal cord and lower brainstem

Answer 49

glycine

Question 50

in the nerve terminal, glutamine is converted to glutamate via ___________ in the mitochondrial membrane

Answer 50

gutaminase

Question 51

glutamate release behaves like ____ at the nerve treminal. Increased intracellular ____ triggers what?

Answer 51

behaves much like Ach at the nerve terminal. increased intracellular Ca2+ triggers vesicle fusion.

Question 52

glutamate removal in nerve terminal (1 way, 2 locations)

Answer 52

- reuptake of glutamate in nerve terminals occurs via glutamate transporters - glial cells also reuptake glutamate from synaptic cleft via glutamate transporters

Question 53

3 types of glutamate receptors (that can be inotropic or metabatropic)

Answer 53

1. NMDA (n methyl d aspartate) 2. alpha amino 3 hydroxy 5 methyl 4 isoxazole propionate receptors (AMPAR) 4. kainate receptors.

Question 54

full activation of NMDA receptors includes binding of what

Answer 54

binding of two glutamates, two glycines, and a depolarizing voltage change.

Question 55

neuronal injury initiated by excessive glutamate release (excitotoxicity) is the pathologic mechanism in the following diseases (6)

Answer 55

huntingtons alzeimhers ALS stroke and trauma hyperalgesia epilepsy

Question 56

which enzyme catalyzes the decarboxylation of glutamate to GABA

Answer 56

glutamic acid decarboxylase (GAD). amount of GABA correlates to amount of functional GAD

Question 57

two inhibitory neurotransmitters in nervous system include

Answer 57

GABA and glycine

Question 58

GABA synthesis

Answer 58

1. glutamine enters presynaptic nerve terminal through glutamine transporter 2. in mitochondria, glutaminase converts glutamine to glutamate 3. back in cytoplasm, GABA is formed by decarboxylation of glutamate. reaction is catalyzed via GAD. 4. GABA is transported into vesicles via H+ antiporter then stores in vesicles until release

Question 59

GABA removal

Answer 59

- taken into presynaptic terminal via GABA transporters and repackaged into vesicles aka its recycled. - also taken up into glial cells via GABA transporters. - in glia, GABA is converted to glutamate by mitochondrial enzyme, GABA transaminase

Question 60

this enzyme converts glutamate to glutamine

Answer 60

glutamine synthetase

Question 61

GABA A receptors (inotropic) receptor type activated by target of (7)

Answer 61

ligand gated Cl- channels activated by binding of two GABA molecules target of benzos, barbs, propofol, etomidate, volatiles, neurosteroids, flumazenol

Question 62

GABA B receptors (metabatropic) receptor type activated causes target of

Answer 62

GPCR inhibitory effects in post synaptic neurons via second messenger systems Gi, inhibits adenylyl cyclase, Beta-gamma unit opening of K channels and Beta-gamma closing of Ca2+ channels Example: baclofen

Question 63

are glycine receptors inotropic, metabatropic, or both

Answer 63

only inotropic

Question 64

magnesium ions block this channel at Resting membrane potential

Answer 64

NMDA

Question 65

what two binding sites are located in NMDA receptor channel (pore)

Answer 65

Mg2+ ketamine/PCP

Question 66

NE and epi are metabolized to vanillylmandelic acid by

Answer 66

catechol O methyltransferase (COMT) and monoamine oxidase (MAO)

Question 67

5 biogenic amine neurotransmitters. Which is the only inotropic receptor?

Answer 67

1. DA 2. NE 3. Epi 4. serotonin (the only inotropic receptor) 5. histamine

Question 68

all catecholamines are synthesized from

Answer 68

tyrosine

Question 69

Serotonin is synthesized from

Answer 69

tryptophan *5-H**T**3*

Question 70

Step 1 to create catecholamines: starts with ____ and ____ converts it to tyrosine

Answer 70

Starts with Phenylalanine and phenylalanine hydroxylase converts it into tyrosine

Question 71

Step 2 to create catecholamines: tyrosine is hydroxylated to form ____ by the enzyme ____ What is important about this step?

Answer 71

tyrosine is hydroxylated to form L-DOPA by the enzyme Tyrosine Hydroxylase **this is the rate limiting step in catecholamine synthesis**

Question 72

Step 3 to create catecholamines: what happens to L dopa to yield dopamine

Answer 72

decarboxylated (CO2 removed) by aromatic L amino acid carboxylase

Question 73

Step 4 to create catecholamines: what enzyme catalyzes the hydroxylation of dopamine to form NE

Answer 73

dopamine beta hydroxylase

Question 74

Step 5 to create catecholamines: what enzyme catalyzes the methylation (CH3) of NE to form epi

Answer 74

NE moves out of vescicles back into cytoplasm and phentolamine n methyltransferase (PNMT) catalyzes the methylation of NE to epi

Question 75

MAO-A preferentially degrades (3)

Answer 75

dopamine epi serotonin

Question 76

MAO-B degradation specs (preference)

Answer 76

degrades dopamine more rapidly than serotonin and NE

Question 77

end product of catecholamine metabolism

Answer 77

vanillylmandelic acid. (eliminated via urine)

Question 78

major metabolite of dopamine

Answer 78

homovanillic acid (also ecreted in the urine)

Question 79

histidine is ________ to form histamine

Answer 79

decarboxylated

Question 80

what enzymatic reaction is present in ALL biogenic amine neurotransmitter biosynthesis?

Answer 80

decarboxylation

Question 81

largest concentration of Dopaminergic neurons in brain is located in

Answer 81

substantia niagra ## Footnote these neurons are crutial for movement, degeneration can cause Parkinson's disease

Question 82

major concentration of noradrenergic (NE) neurons in CNS is

Answer 82

locus coeruleus in the pons ## Footnote noradrenergic neurons reach the thalamus, hypothalamus, limbic system and cerebral cortex

Question 83

two major group locations of adrenergic (epi) neurons in CNS are

Answer 83

rostral ventrolateral medulla Nucleus Tracutus Solitarius

Question 84

serotonin synthesis

Answer 84

Question 85

metabatropic serotonin receptors and what they activate (3)

Answer 85

5HT1 inhibit adenylyl cyclase 5HT2 stimulate PLC and mobilization of Ca2+ 5HT4 stimulate adenylyl cyclase and PKA activation

Question 86

inotropic serotonin receptor and what it activates

Answer 86

5HT3R- nonselective cation channel. block receptors in area postrema and vagus nerve which normally activates vomiting center

Question 87

NE preferentially binds to

Answer 87

a1, a2, b1

Question 88

A1 receptors are coupled with ____ which activates ______ and subsequent downstream reactions

Answer 88

Gq, Phospholipase C

Question 89

Alpha2 receptors are coupled with ____ which inhibits ____ and reduces ____ production

Answer 89

Gi, Adenylyl cyclase, cAMP

Question 90

beta adrenergic receptors are coupled to ____ which activates _________ and increases ________ production

Answer 90

Gs, Adenylyl cyclase, cAMP

Question 91

NOS catalyzes the oxidation of ____ to ____ and NO (end byproducts)

Answer 91

L arginine (the substrate) L citrulline

Question 92

NO is a universal intercellular messenger, acting as both an ___________ and ____________ signaling molecule

Answer 92

autocrine and paracrine

Question 93

NO synthesis

Answer 93

1. glutamate is released from the presynaptic nerve terminal by Ca2+ dependent exocytosis 2. glutamate acts on NMDA receptors located on post synaptic neuron, and Ca2+ enters the post synaptic neuron and binds with calmodulin 3. Ca2+ calmodulin complex activates NO Synthesis 4. activation of NOS results in the formation of NO and citrulline from L arginine 5. NO interacts with heme cofactor of soluble guanylate cyclase resulting in activation 6. activated sGC catalyzes conversion of GTP to cGMP in post synaptic neuron. increased levels of cGMP in post synaptic neuron result in physiologic effect

Question 94

NO release from post synaptic neurons

Answer 94

1. retrograde diffusion of NO into presynaptic terminal is believed to result in enhanced and prolonged NT release from presynaptic neuron (positive feedback) 2. NO can also diffuse out to the neighboring neurons. NO stimulates soluble guanylate cyclase and increases cGMP levels 3. NO can also diffuse out to adjacent glial cells. in glial cells, NO also stimulates sGC and increases cGMP levels

Question 95

NO termination

Answer 95

highly reactive free radical, having a half life of only a few seconds. cell signaling function of NO are terminated when NO is converted to nitrites* and nitrates* by O2 an H2O

Question 96

NO is synthesized and released by ____________

Answer 96

endothelial cells

Question 97

GTP and ATP are classified as

Answer 97

purines

Question 98

what enzyme converts ATP to adenosine in synaptic cleft

Answer 98

ectonucleotidase

Question 99

are all neuro peptide receptors inotropic or metabatropic?

Answer 99

metabatropic

Question 100

insulin and growth factors are endogenous ligands for which receptor

Answer 100

receptor tyrosine kinase (RTK)

Question 101

leptin and most other cytokines are endogenous ligands for

Answer 101

tyrosine kinase associated receptors

Question 102

natriuretic peptides are hormone ligands for which receptor

Answer 102

guanylyl cyclases

Question 103

transmembrane catalytic receptors or enzyme linked receptors definition

Answer 103

transduce an extracellular ligand binding interaction into intracellular effect by activating linked enzymatic domain ## Footnote An enzyme-linked receptor is a specialized cell-surface receptor that, upon binding a ligand, either acts as an enzyme itself or directly activates an associated enzyme inside the cell. Unlike G protein-coupled receptors that use an intermediate "messenger" protein, these receptors bridge the gap between the outside and inside of the cell by triggering enzymatic activity directly.

Question 104

5 major categories of enzyme linked receptors

Answer 104

1. receptor guanylyl cyclases contain systolic domain that catalyzes formation of cGMP from GTP 2. receptor tyrosine kinases are largest group of transmembrane catalytic receptors 3. tyrosine kinase associated receptors lack inherent catalytic activity. recruit active cystolic signaling proteins in ligand dependent manner 4. receptor serine/threonine kinases: have intrinsic catalytic activity. phosphorylate serine and threonine residues on target cytosolic proteins 5. receptor tyrosine phosphates: dephosphorylate tyrosine residue on other transmembrane receptors or on cytosolic proteins.

Question 105

The Insulin receptor tyrosine kinase (RTK)

Answer 105

Each monomer has 2 polypeptide chains (alpha and beta) held together by disulfide bonds. the two monomers held together by the disulfide bond create a dimer (pair) * insulin binding activates the tyrosine kinase domain leading to autophosphorylation and the insuline receptor substrate (IRS)

Question 106

What types of signaling molecules can enter the cell and bind with intracellular (nuclear) receptors?

Answer 106

- Steroid hormones - Prostaglandins - Vitamin D - Thyroid hormones - retinoic acid

Question 107

T4 is usually converted to T3 by

Answer 107

deiodinase ## Footnote the thyroid receptor can bind to T4, but the nucleus of the cell has a 10x greater affinity for T3

Question 108

3 forms of cell death

Answer 108

- apoptosis - necrosis - autophagic cell death

Question 109

State the features of the cell experienceing necrosis - processes - cell size - nucleus - plasma membrane - cellular contents - adjacent inflammation?

Answer 109

- processes: uncontrolled - cell size: enlarged (swelling) - nucleus: pyknosis to karyolysis - plasma membrane: disrupted - cellular contents: enzymatic digestion - may leak out of cell - adjacent inflammation?: frequent

Question 110

State the features of the cell experienceing apoptosis - processes - cell size - nucleus - plasma membrane - cellular contents - adjacent inflammation?

Answer 110

- processes: generally programmed - cell size: reduced (cell shrinks) - nucleus: fragmentation into nucleosome sized fragments - plasma membrane: intact - altered structure - cellular contents: intact - adjacent inflammation?: no

Question 111

2 pathways that initiate apoptosis and the summary of each

Answer 111

1. **Intrinsic (mitochondrial) pathway**: damamge to the mitochondria by reactive oxygen species or increases in Ca++ will result in Bax/Bak channels opening. Cytochrome C and other proteins leak though causing swelling and rupture 2a. **Extrinsic (death receptor-initiated) pathway**: extracellular signals bind to a transmembran death receptor. Undergoes autoproteolytic cleavage releasing active caspase-8 2b. **Executioner (death) pathway**: executioner caspases are proteolytic enzymes that degrade cellular components - *especially nucleus* - into small fragments. Cell components are then packaged into "bite-sized" apoptotic bodies and eaten by phagocytes (dead cells disappear in minutes)

Question 112

in the presynaptic nerve terminal, opioid activated GPCR beta-gamma subunits block

Answer 112

VgCa++ channels ## Footnote block voltage gated Ca++ channels in the presynaptic terminal leading to decreased Ca++ and reduced neurotransmitter realse

Question 113

B1 receptor helps cardiac performance in at least 4 ways

Answer 113

inotropy chronotropy lucitropy (relaxation) dromotropy (conduction velocity)

Question 114

how does B1 receptor activation in SA and AV node lead to positive chronotropy and dromotropy

Answer 114

- In SA nodal cells: phosphorylation of L type Ca2+ channels and phospholamban lead to increased intracellular Ca2+ which leads to increased rate of phase 4 depolarization. (positive chronotropy) - In AV nodal cells: same pathway enhances excitability and firing and thus dromotropy

Question 115

NO mediated vascular smooth muscle relaxation (7 steps)

Answer 115

1. stress, Ach, histamine, bradykinin, 5HT, substance P, ATP increase intracellular Ca2+. 2. Ca2+ combines with calmodulin (CaM) and the Ca/CaM complex activates endothelial NOS (eNOS) 3. eNOS produces NO from L arginine. NO diffuses to Vascular smooth m. cells 4. NO in smooth m. cells activate soluble guanylyl cyclase (sGC), which catalyzes conversion of GTP to cGMP 5. cGMP activates downstream effects promoting smooth muscle relaxation and vasodilation 6. NO also activates K channels leading to increased K efflux and hyperpolarization of cell membrane,. 7. net effect is relaxation of smooth muscle cell

Question 116

3 drugs that donate NO directly to Vascular smooth m. cell's

Answer 116

nitroglycerine, Na nitroprusside, isosorbide dinitrate

Question 117

presynaptic inhibitory response of opioids

Answer 117

Gbeta-gamma subunits block VgCa channels. - decreased Ca2+ influx in presynaptic terminal leads to reduced NT release and suppression of synaptic communication

Question 118

postsynaptic inhibitory response to opioids

Answer 118

Galpha-inhibitory subunits: - inhibition of adenylyl cyclase and cAMP production and PKA activation resulting in modulation of VgNa channels. - activate inwardly rectifying K+ channels (GIRK) leading to hyperpolarization of post synaptic membrane. - activate protein kinase cascades and DNA transcription taken together, the post synaptic responses to opioids are decreased excitability and potential long term tolerance to opioids

Question 119

vasopressin has two other names

Answer 119

arginine vasopressin (AVP) and of course ADH ## Footnote Thanks Schmidt :'(

Question 120

vasopressin pathway at the nephron

Answer 120

* vasopressin binds to V2 GPCR's on basolateral membrane activating Gs protein * Gs stimulates adenylyl cyclase to produce cAMP. * cAMP activates PKA * PKA phosphorylates H2O channel aquaporin 2 (AQP2) and activates transport and fusion of aquaporin containing vesicles in apical membrane increased APQ2 in apical membrane increases water reabsorption regulation of water reabsorption in collecting duct modulates urine and plasma osmolality and intravascular volume *AVP also binds to V1 receptors on vascular smooth m. which activates Gq*

Question 121

PDE3 binds to ____ and is found in (4)

Answer 121

binds to cAMP and cGMP but has 10x the affinity for cAMP - found in heart, Vascular smooth m., and placental smooth muscle and tissues important in energy homeostasis (liver, pancreatic beta cells, adipocytes)

Question 122

2 drugs that are selective PDE3 inhibitors

Answer 122

milrinone and amrinone

Question 123

what happens when PDE3 is inhibited

Answer 123

- increases cAMP levels and prolongs downstream signaling effects. - in heart: promotes positive chronotropy, dromotropy, inotropy, lusitropy - in VSMC, increased cAmP leads to vasodilation

Question 124

milrinone is used to tx (3) and elimination

Answer 124

pHTN, cerebral vasospasm after aneurysmal SAH, neonatal septic shock eliminated by renal excretion (80% unchanged)

Question 125

PDE5 binds to ____ is found in (3)

Answer 125

cGMP selective found in tissue throughout the body with higher levels in corpus cavernous (erectile tissue of peepee and clitoris), Vascular smooth m. cells's, and platelets

Question 126

medications that are PDE5 inhibitors (3) and what they're used to tx (4)

Answer 126

"afil" sildenafil, vardenafil, tadalafil tx: ED, pHTN, high altitude sickness, memory dysfunction

Question 127

PDE5 inhibitors are metabolized by

Answer 127

CYP450 3A4 in the liver

Question 128

PDE4 binds to ____ and is found in

Answer 128

cAMP selective modulates B2 adrenergic responses in pulmonary smooth muscle

Question 129

PDE4 drug used for COPD and metabolism of drug

Answer 129

roflumilast undergoes extensive hepatic metabolism by both phase 1 and 2 reactions

Question 130

What is a class of drug that is a weak, nonselective PDE inhibitor

Answer 130

Methylxanthines (caffeine and throphylline)

Question 131

Examples of Positive feedback in the body

Answer 131

- AP generation - Coagulation cascade - Uterine contractions during childbirth

Question 132

How does the positive feedback loop happen with the uterus?

Answer 132

Regulated variable: uterine contractions sweep downward and force feus towards cervix Sensors: stretch receptors in cervix, fetus pressure against cervix opens cervical canal and sensory impulses are sent to hypothalamus Feedback controller: veriventricular and supraoptic nuclei of the hypothalamus stimulate post. pituitary to release more oxytocin Effectors: oxytocin produces more foeceful uterine contractions (stimulating more oxytocin)

Question 133

What is endocrine cell signaling?

Answer 133

Signaling molecule (i.e. hormone) is secreted by an endocrine cell and transported through the circulation where is acts on **distant** target cell

Question 134

What is paracrine signaling?

Answer 134

a chemical signaling molecule is realeased by one cell and acts locally to regulate the neighboring cells (neurotransmitter cells)

Question 135

What is autocrine cell signaling? what are examples?

Answer 135

A cell responds to a signaling molecule it also prodouced itself (NE binds to an alpha-2 receptor on the same nerve terminal that released the NE)

Question 136

What are the 4 classifications of signal transduction?

Answer 136

- Transmembrane G protein-coupled receptors (GPCRs) - Transmembrane ligand-gated ion channels - Transmembrane enzyme-linked receptors - Soluble intracellular (nuclear) receptors

Question 137

What family of enzyes catalyzes the addition of a phosphate group to a molecule?

Answer 137

Kinases

Question 138

When are G proteins turned on and turned off?

Answer 138

They are turned ON when a ligand binds to the receptor-binding site They are turned OFF by the intrinsic GTPase activity in the alpha subunit

Question 139

Steps of activating the GPCR

Answer 139

- Inactive state: GDP is bound to alpha - Ligand binds to the receptor: conformational change, GDP released, and GTP then binds to alpha subunit - alpha-GTP unit breaks free from beta and gamma and interacts with downstream effector(s): can stimulate or inhibit - the beta-gamma unit can also interact with effectors

Question 140

What are the major effector targets of the GTP-alpha subunit?

Answer 140

- Adenylate cyclase - Phospholipase C - Phospholipase A2

Question 141

What are the major effectors beta-gamma subunits can interact with?

Answer 141

- Gi,0 - regulated K+ channels - Voltage gated calcium channels - beta adrenergic receptor kinase

Question 142

What effector is involved with the Gs or Gi GPCR family

Answer 142

adenalate cyclase Gs - stimulated Gi - inhibits

Question 143

What effector is involved with the Gq GPCR family?

Answer 143

Phospholipase C (stimulates)

Question 144

Second messenger of Adenylyl cyclase

Answer 144

ATP to cAMP

Question 145

Second messenger of Phospholipase C

Answer 145

PIP2 to IP3 + DAG

Question 146

What is the second messenger to Phospholipse A2?

Answer 146

Phospholipid + arachidonic acid

Question 147

cAMP effects on each different tissue - cardiac monocytes - smooth muscle airways/vessles - platelets - principal cells of nephron

Answer 147

- cardiac monocytes: increased cAMP enhances contractility (beta1) - smooth muscle airways/vessles: increased cAMP causes relaxaiton and dialation (beta 2) - platelets: reduces platelet aggregation - principal cells of nephron: promotes insertion of aquaporin-2 water channels in the apical membrane

Question 148

cAMP's role in activation of PKA

Answer 148

Protein Kinase A is activated to modify cellular function

Question 149

DAG's role in PKA activation

Answer 149

DAG and Ca++ activate Protein Kinase A causing - receptor desensitazation - modulating membran structure - regulating transctiption - mediating immune responses - regulating cell growth - learning/memorty

Question 150

Role of IP3 and activating Ionized calcium release

Answer 150

IP3 liberates Ca++ from intracellular storage - increased intracellular Ca++

Question 151

Excitatory responses for the membrane usually are produced by a net ____ current. What ions would cause this?

Answer 151

Excitatory responses for the membrane usually are produced by a net **inward** current. **This usually depolarizes the membrane** - Na+ influx - Ca++ influx - reduced K+ efflux

Question 152

Inhibitory responses for the membrane usually are produced by a net ____ current. What ions would cause this?

Answer 152

Inhibitory responses for the membrane usually are produced by a net **outward** current. **this hyperpolarizes the membrane** - increased K+ efflux - Cl- influx - Closure of Ca++ channels

Question 153

What is the rate limiting step for ACh synthesis?

Answer 153

Choline is actively transported into the presynaptic terminal (this transport is the rate limiting step)

Question 154

What caralyzes the formation of ACh? and what is ACh made from?

Answer 154

Choline acetyltransferease (ChAT) catalyzes the formation of ACh from acetyl-CoA and Choline

Question 155

How does acetylcholinesterase (AChE) break down ACh?

Answer 155

AChE hydrolyzes ACh to acetate + choline choline re-enters nerve terminal and is reused for ACh synthesis

Question 156

How many ACh molecules must bind to the N-ACH-R to create the conformational change?

Answer 156

2 One at the extracellular alpha/epasalon interface and one at the alpha/delta subunit (they bind to the alpha)

Question 157

Primaty excitatory neurotransmitter in the brain

Answer 157

Glutamate

Question 158

Primary inhibitory neurotransmitter in the brain

Answer 158

GABA

Question 159

Primary inhibitory neurotransmitter in the spinal cord

Answer 159

Glycine

Question 160

Where is glutamate synthesized?

Answer 160

It is synthesized in the brain since it does not cross the BBB ## Footnote the brain can convert GABA to glutamate and vice versa