Lecture 6 (Respiration) Flashcards
What do each of these receptors do? (3)
Gq
Gs
Gi
Gq receptors linked to contraction
Gs linked to relaxation
Gi oppose relaxation process
Describe the process of smooth muscle contraction? (5)
- Increase in intracellular calcium
-Binds to calmodulin
-You have activated calcium calmodulin which activates MLCK
-MLCK phosphorylates myosin chain which causes contraction
-Smooth muscle remain contracted while MLCK is phosphorylated
How do you reverse smooth muscle contraction?
MLCP relaxes smooth muscle
(doesn’t reverse with less calcium)
What are the 3 classes of Gq receptor? (3)
M3 Muscarinic receptors
H1 Histamine receptors
BK bradykinin receptors (g protein coupled)
What are the 3 classes of Gq receptor? (3)
M3 Muscarinic receptors
H1 Histamine receptors
BK bradykinin receptors (g protein coupled)
What happens when agonist binds to receptor (Gq)? (3)
-Agonist binds to receptor, activates G protein
-Leads to stimulated phospholipase C
-Which breaks down PIP2 into DAG and IP3
What are the short term effects after agonist binds to receptor (Gq)? (5)
Short term effects ->
-Muscle contraction, IP3 will act on IP3 receptors leads to release of calcium
-From the source calcium binding to calmodulin
-Activation of MLCK and contraction of the muscle
-We reduce the airway diameter
-Increases resistance of airflow makes it harder to breathe
(More effort required for breathing)
What are the long term effects after agonist binds to receptor (Gq)? (2)
Long term effects ->
-DAG stimulates protein kinase C
-Protein kinase C has longer term effects on muscle cell which leads to remodelling of airway smooth muscle
What happens when agonist binds to receptor (Gs)? (8)
-Stimulation of adenylate cyclase
-Camp is then formed
-This activates protein kinase A which has various effect on cell
-One of the effects is stimulation of potassium channels
-Potassium efflux into cell, hyperpolarized membrane, makes membrane potential away from voltage calcium channels opening
-Inhibits MLCK, activation of MLCP
-Diameter increases
-Decreases in resistance to airflow, so easier to breathe
What are the long term effects of agonist binding to Gs?
-Inhibit remodeling growth, of muscle cells
Explain the control of airway smooth muscle via Gi? (4)
-Activation of Gi receptors leads to inhibition of Adenylate Cyclase
-Knock on effect of this is to counteract the stimulatory effect of Gs activation
-Opposes the relaxation of the smooth muscle
-Also inhibits the BK potassium channel
What receptors act through Gi pathway?
M2 Muscarinic receptors
Where do you find M2 receptors?
On post ganglionic nerve fibers
What receptors are found on blood vessels?
M3
What receptors are found on smooth muscle cells?
M3 (some may have M2)
What receptors are found on epithelial cells? (2)
We have M1 and M3 on epithelial cells, stimulation of these is due to mucus secretion
What happens when M3 receptors are activated? (4)
M3 receptors on smooth muscle
Are activated
-Stimulates phospholipase 3
-IP3 causes calcium release
-MLCK activation
-Phosphorylation of MLC causes contraction
Describe auto-inhibition for hypersensitivity inn airways? (3)
Auto-inhibition (negative feedback mechanism) –
-Ach is released at nerve terminal, some of it will interact with the M2 receptors on post–ganglionic nerve
-Activation of these receptors inhibits/reduces further release of Ach
-Negative feedback mechanism to prevent overstimulation/contraction of smooth muscle
Detects feedback in hypersensitivity of the airways
What does B2 agonist do? (4)
-Acts on receptor which stimulates adenylate cyclase
-Camp production had genomic effect, reduces inflammation and proliferation, inhibits MLCK, stimulates BK potassium channels (hyperpolarize membrane)
-Increases activity of sodium calcium exchanges (you remove calcium form the cytoplasm)
-Helps lower calcium levels so you have less muscle contraction
What is Noradrenergic/noncholinergic (NANC) signalling?
Noradrenergic/NonCholinergic (NANC) nervous system present in airways but importance in humans is unestablished and controversial
What are the two pathways of NANC signalling? (2)
– excitatory or eNANC - bronchoconstriction
transmitters: Substance P/Neurokinin A (SP/NKA)
- inhibitory or iNANC - bronchorelaxation (dilation)
transmitters: Vasointestinal Peptide (VIP)
Nitric Oxide
Neuropeptide Y (NPY)
What is Athsma?
“a common chronic disorder of the airways that is complex and characterised by variable and recurring symptoms, airflow obstruction, bronchial hyper-responsiveness, and an underlying inflammation.”
What are the two types of asthma? (2)
Atopic (extrinsic)
Non-Atopic (intrinsic)
What is Atopic (extrinsic) asthma?
Atopic (extrinsic) – Associated with allergies. Linked to elevated levels of serum IgE and positive skin-prick test.
Presentation of allergen leads to activation of mast cells. Release of inflammatory mediators including histamine.
Can lead to activation of other inflammatory cells such eosinophils.