Lecture 7 & 8 Signaling Flashcards
Signaling through cell to cell contact
Give examples
Contact signaling
(antigen presentation to t cells, membrane bound signal molecule)
communication between muscle cells, through second messengers)
Short distance signaling between different cells
Give example
Paracrine signaling (Cytokines, low concentration, short half life, high affinity) (Neurotransmitters, high concentration, short half life, low affinity)
Short distance signaling involving the same (or same type of) cell(s)
Give example
Autocrine signaling
Prostaglandin
Long distance signaling between endocrine glands and target cells
Endocrine signaling (Long half life due to long distance to travel)
ACh receptors located in skeletal muscle, type of receptor?
Nicotinic ACh receptor
Na+/K+ channel (ion channel receptors)
ACh receptors located in heart muscle, type of receptor?
Muscarinic ACh receptor
G protein-linked receptor
enzyme that degrades excess ACh
Acetylcholine esterase
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
Myasthenia gravis
How to manage Myasthenia gravis?
Increase ACh signaling, Since the autoantibodies attack nicotinic ACh receptors, not enough signaling is happening. Inhibiting acetylcholine esterase will increase signaling.
What medications help treat myasthenia gravis?
-stigmine drugs
pyridostigmine, neostigmine
and physostigmine, all reversible.
They inhibit ACh esterase
How do organophosphates (Certain insecticides Nerve gases (Sarin, VX)) cause death?
They inhibit ACh esterase causing too much
ACh to be in the synapse, too much signaling.
How do you treat exposure to organophosphates (Certain insecticides Nerve gases (Sarin, VX))?
Decrease signaling of ACh by inhibiting muscarinic ACh receptors.
What medication help treat exposure to organophosphates (Certain insecticides Nerve gases (Sarin, VX))?
Atropine, which inhibits ACh receptors.
Where are Type I and III nuclear receptors located and what do they bind?
Type I and III receptors are localized in the cytosol, they bind with steroid hormones (Cortisol, Aldosterone Progesterone, Testosterone, Estradiol)
An anti-inflammatory steroid drug that acts through this signaling pathway. It is ~ 30 times more efficient than the naturally occurring steroid hormone, cortisol.
Dexamethasone
Where are Type II nuclear receptors located and what do they bind?
Type II intracellular receptors are localized in the nucleus
They bind with Vitamin D3, retinoic acid, thyroid hormone, and fatty acids
These drugs activate an intranuclear fatty acid receptor (PPARγ) and increase insulin sensitivity. They are used to manage Type II diabetes.
Thiazolidinediones (TZDs)
What drugs use nitric oxide to cause vasodilation
nitroglycerin, nitroprusside and hydroxyurea
G protein linked receptors that Regulate heart-rate, smooth muscle constriction, metabolism
Adrenergic (epinephrine, norepinephrine) receptors
Dopamine receptor is a major pharmacological target in treatments of which diseases?
Schizophrenia, Parkinson’s disease, Attention deficit disorders.
Enzyme that adds phosphate group
Enzyme that removes phosphate group
Kinase (requires ATP)
Phosphatase
What type of receptors use second messengers?
G-protein linked receptors
What do second messengers activate?
Protein kinases
Gα subunit, stimulates adenylyl cyclase, increases cAMP
Gs,α
Gα subunit, inhibits adenylyl cyclase, decreases cAMP
Gi/o,α
Gα subunit, activates phospholipase Cβ, increases DAG, IP3 and Ca2+
Gq,α
Gα subunit, stimulates phosphodiesterase, decreases cGMP
Gt,α
Stimulatory hormones
Epinephrine, Glucagon, Adrenocorticotrophic hormone (ACTH)
Inhibitory hormone
Prostaglandin E1 (PGE1), Adenosine
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.
Cholera toxin
Stimulates stimulator
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.
Pertussis toxin
Inhibites inhibitor
How does cAMP activate protein kinase A
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).)
α1-adrenergic receptors on smooth muscle cells mediate vasoconstriction through this mechanism.
Protein phospholipase Cβ
These are used in decongestants and eye drops
α1-adrenergic agonists
Role of phosphodiesterase
Activated by rhodopsin from phototransduction. Phosphodiesterase hydrolyzes cGMP to GMP (degrades 2nd messenger!) The fall in cGMP levels closes cGMP-gated ion channels
How does caffeine increase heart rate?
Caffeine is an antagonist of the adenosine receptor and increases heart rate. (Adenosine lowers heart rate)
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.
Tyrosine kinase receptors
Glucose transporter (GLUT4) is shuttled to the plasma membrane to enhance glucose uptake by muscles and adipose tissue in this pathway
PI 3-kinase pathway . (PI3K)
Pathway where transcription and translation is regulated in for genes necessary for glucose metabolism
MAP-Kinase pathway (MAPK)
Pathway where excess glucose can be stored in glycogen or fatty acids (lipids)
Phospholipase Cγ pathway (PLCγ)
Activating an intracellular peroxisome proliferator activated receptor (PPAR) induces the transcription of genes involved in glucose metabolism, treatment for what disease?
Type II diabetes
What enzyme destroys cAMP, cGMP
Phosphodiesterase
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?
Hyperthyroidism (Grave’s disease)
