Lecture 7 & 8 Signaling

Question 1

Signaling through cell to cell contact

Give examples

Answer 1

Contact signaling
(antigen presentation to t cells, membrane bound signal molecule)
communication between muscle cells, through second messengers)

Question 2

Short distance signaling between different cells

Give example

Answer 2

Paracrine signaling
(Cytokines, low concentration,  short half life, high affinity)
(Neurotransmitters, high concentration, short half life, low affinity)

Question 3

Short distance signaling involving the same (or same type of) cell(s)
Give example

Answer 3

Autocrine signaling

Prostaglandin

Question 4

Long distance signaling between endocrine glands and target cells

Answer 4

Endocrine signaling
(Long half life due to long distance to travel)

Question 5

ACh receptors located in skeletal muscle, type of receptor?

Answer 5

Nicotinic ACh receptor

Na+/K+ channel (ion channel receptors)

Question 6

ACh receptors located in heart muscle, type of receptor?

Answer 6

Muscarinic ACh receptor

G protein-linked receptor

Question 7

enzyme that degrades excess ACh

Answer 7

Acetylcholine esterase

Question 8

Autoimmune neuromuscular disease (muscle weakness, muscle fatigue) Autoantibodies against the nicotinic ACh receptors

      - inhibit ACh binding to the receptor
      - enhance the internalization and destruction of the receptor

Answer 8

Myasthenia gravis

Question 9

How to manage Myasthenia gravis?

Answer 9

Increase ACh signaling, Since the autoantibodies attack nicotinic ACh receptors, not enough signaling is happening. Inhibiting acetylcholine esterase will increase signaling.

Question 10

What medications help treat myasthenia gravis?

Answer 10

-stigmine drugs
pyridostigmine, neostigmine
and physostigmine, all reversible.
They inhibit ACh esterase

Question 11

How do organophosphates (Certain insecticides
Nerve gases (Sarin, VX)) cause death?

Answer 11

They inhibit ACh esterase causing too much

ACh to be in the synapse, too much signaling.

Question 12

How do you treat exposure to organophosphates (Certain insecticides Nerve gases (Sarin, VX))?

Answer 12

Decrease signaling of ACh by inhibiting muscarinic ACh receptors.

Question 13

What medication help treat exposure to organophosphates (Certain insecticides Nerve gases (Sarin, VX))?

Answer 13

Atropine, which inhibits ACh receptors.

Question 14

Where are Type I and III nuclear receptors located and what do they bind?

Answer 14

Type I and III receptors are localized in the cytosol, they bind with steroid hormones (Cortisol, Aldosterone Progesterone, Testosterone, Estradiol)

Question 15

An anti-inflammatory steroid drug that acts through this signaling pathway. It is ~ 30 times more efficient than the naturally occurring steroid hormone, cortisol.

Answer 15

Dexamethasone

Question 16

Where are Type II nuclear receptors located and what do they bind?

Answer 16

Type II intracellular receptors are localized in the nucleus

They bind with Vitamin D3, retinoic acid, thyroid hormone, and fatty acids

Question 17

These drugs activate an intranuclear fatty acid receptor (PPARγ) and increase insulin sensitivity. They are used to manage Type II diabetes.

Answer 17

Thiazolidinediones (TZDs)

Question 18

What drugs use nitric oxide to cause vasodilation

Answer 18

nitroglycerin, nitroprusside and hydroxyurea

Question 19

G protein linked receptors that Regulate heart-rate, smooth muscle constriction, metabolism

Answer 19

Adrenergic (epinephrine, norepinephrine) receptors

Question 20

Dopamine receptor is a major pharmacological target in treatments of which diseases?

Answer 20

Schizophrenia, Parkinson’s disease, Attention deficit disorders.

Question 21

Enzyme that adds phosphate group

Enzyme that removes phosphate group

Answer 21

Kinase (requires ATP)

Phosphatase

Question 22

What type of receptors use second messengers?

Answer 22

G-protein linked receptors

Question 23

What do second messengers activate?

Answer 23

Protein kinases

Question 24

Gα subunit, stimulates adenylyl cyclase, increases cAMP

Answer 24

Gs,α

Question 25

Gα subunit, inhibits adenylyl cyclase, decreases cAMP

Answer 25

Gi/o,α

Question 26

Gα subunit, activates phospholipase Cβ, increases DAG, IP3 and Ca2+

Answer 26

Gq,α

Question 27

Gα subunit, stimulates phosphodiesterase, decreases cGMP

Answer 27

Gt,α

Question 28

Stimulatory hormones

Answer 28

Epinephrine, Glucagon, Adrenocorticotrophic hormone (ACTH)

Question 29

Inhibitory hormone

Answer 29

Prostaglandin E1 (PGE1), Adenosine

Question 30

This toxin transfers an ADP-ribose group to a stimulatory Gsα subunit (post-translational modification). - The adenylyl cyclase remains constantly active (lots of cAMP) - It causes extreme salt and water efflux from gut epithelial cells to the lumen, causing diarrhea.

Answer 30

Cholera toxin | Stimulates stimulator

Question 31

This toxin transfers an ADP-ribose group to an inhibitory Giα subunit (post-translational modification). - Adenylyl cyclase cannot be inhibited (lots of cAMP). - It leads to increased mucus secretion in airway epithelium.

Answer 31

Pertussis toxin | Inhibites inhibitor

Question 32

How does cAMP activate protein kinase A

Answer 32

Binding cAMP to the regulatory subunits dissociates the subunits of protein kinase A and activates the catalytic subunits. (The catalytic subunits then phosphorylate target proteins (using ATP).)

Question 33

α1-adrenergic receptors on smooth muscle cells mediate vasoconstriction through this mechanism.

Answer 33

Protein phospholipase Cβ

Question 34

These are used in decongestants and eye drops

Answer 34

α1-adrenergic agonists

Question 35

Role of phosphodiesterase

Answer 35

Activated by rhodopsin from phototransduction. Phosphodiesterase hydrolyzes cGMP to GMP (degrades 2nd messenger!) The fall in cGMP levels closes cGMP-gated ion channels

Question 36

How does caffeine increase heart rate?

Answer 36

Caffeine is an antagonist of the adenosine receptor and increases heart rate. (Adenosine lowers heart rate)

Question 37

Receptors used by many growth factors and insulin -Can activate multiple intracellular signaling pathways - Mitogen activated protein (MAP)-kinase pathway. - Phospholipase Cγ (PLC γ) pathway. - Phosphatidylinositol-3’-kinase (PI 3-kinase) pathway.

Answer 37

Tyrosine kinase receptors

Question 38

Glucose transporter (GLUT4) is shuttled to the plasma membrane to enhance glucose uptake by muscles and adipose tissue in this pathway

Answer 38

PI 3-kinase pathway . (PI3K)

Question 39

Pathway where transcription and translation is regulated in for genes necessary for glucose metabolism

Answer 39

MAP-Kinase pathway (MAPK)

Question 40

Pathway where excess glucose can be stored in glycogen or fatty acids (lipids)

Answer 40

Phospholipase Cγ pathway (PLCγ)

Question 41

Activating an intracellular peroxisome proliferator activated receptor (PPAR) induces the transcription of genes involved in glucose metabolism, treatment for what disease?

Answer 41

Type II diabetes

Question 42

What enzyme destroys cAMP, cGMP

Answer 42

Phosphodiesterase

Question 43

Autoantibodies stimulate TSH receptors in the thyroid gland  increased thyroid hormone production Thyroid hormone downregulates TSH production but has no effect on autoantibodies The negative feedback does not work  runaway thyroid gland What disease is this?

Answer 43

Hyperthyroidism (Grave’s disease)