L6 - Respiration III - Control of Airway Smooth Muscle Flashcards
Contraction of smooth muscle
- intracellular calcium levels increase.
- Calcium binds to calmodulin - Ca+/Calmodulin
complex is activated. - Ca+/Calmodulin complex stimulates MLCK by
phosphorylation. - MLCK phosphorylates the MLC causing
contraction. - MLC phosphatase dephosphorylates MLC leading
to relaxation.
What receptors are linked to contraction?
Gq - Receptors
What receptors are linked to relaxation?
Gs - Receptors
What receptors inhibit the relaxation process?
Gi Receptors
What receptors act through the Gq pathway?
M3 - Muscarinic Receptors
H1 - Histamine Receptors
Bk - Bradykinin Recepors
What receptors act through the Gs pathway?
B2 adrenergic receptors
VIP Receptors
What drug acts as an agonist on Gs Receptors?
Salbutamol
What happens when the Gs pathway is activated?
Adenylate cyclase is stimulated leading to the formation of cAMP which causes downstream efffects that cause the activation of protein kinase A.
What is a downstream effect of the Gs pathway stimulation?
Stimulation of potassium channels, hyperpolarising the membrane.
what does the activation of Gi receptors cause?
Inhibition of adenylate cyclase.
Opposes the relaxation of smooth muscle.
Also inhibits the Bradykinin Potassium channel
Where are the M1-3 receptors located for parasympathetic control?
- M2 - Postganglionic Nerve
- M2 and M3 - Airway smooth muscle
- M1 and M3 - Epithelial Cells
What receptor is muscle contraction controlled by?
M3
Activation of M3 receptors
Causes muscle contraction - Ach is released at the nerve terminal, some of which will interact with M2 receptors - inhibiting Ach and preventing overstimulation.
What receptor is responsible for parasympathetic contol?
B2 adrenoreceptor
How does a B2 agonist (eg. Salbutamol) work?
- Acts on the receptor stimulating adenylate cyclase and the prodcution of cAMP reducing inflammation.
- Also reduces MLCK and stimulating the potasssium channel, hyperpolarising the membrane and reducing calcium influx.
- All leading to relaxation.
What are the 2 types of asthma?
Atopic (extrisic)
- Associated with allergies, linked to elevated levels of serum IgE
Non- Atopic (intrinsic)
- Induced by various factors such as excersise, cold air, inhaled irritants, stress and drugs.
What are the 2 types of asthma?
Atopic (extrisic)
- Associated with allergies, linked to elevated levels of serum IgE
Non- Atopic (intrinsic)
- Induced by various factors such as excersise, cold air, inhaled irritants, stress and drugs.
What type of activity increase in asthma associated with?
Parasympathetic increase
- manifests as an increase in basal tone and increased muscle constriction
What is the change in M2 function linked toin the case of antigen challenge?
Eosinonopils
Where are eosinophils and where are they mainly located?
A variety of white blood cells that cluster around nerve endings.
What do activated eosinophils release?
Major basic protein (MBP) which inhtibit M2 receptors.
What can be used to treat asthma?
Anticholinergics - Block the effects of ACh
- Competitive inhibitors of M1-3
receptors.
- Help reverse the effect of
brochoconsriction
What is a short-lasting anticholinergic?
Ipratropium - used with short lasting B2 adrenoreceptor agonists as an add on therapy.
What is a long lasting anticholinergic?
Tiotropium - Used in combination with long lasting
