Nicotinic Acetylcholine receptors

Question 1

neuronal nAChR contain how many subunits?

Answer 1

5 subunits that are alpha, beta or all alpha

Question 2

how many types of alpha and beta subunits do neurons express?

Answer 2

neurons express at least nine alpha subunits (alpha2-alpha10) and three beta subunits (beta2-beta4)

Question 3

what properties does the association between different alpha and beta subunits confer?

Answer 3

a mutiltude of nAChRs that differ in their ion-gating and ligand-binding properties

Question 4

what type of nAChR subunit do human bronchial epithelial cells express and what is function?

Answer 4

human bronchial epithelial cells express functional nAChR of the alpha3 subtype which modulate cell shape and affect cell-cell contact (supports concept that nAChR modulate cellular functions other than synaptic transmission)

Question 5

acetylcholinesterase catalyzes the formation of…

Answer 5

ACh–>Choline and Acetate

Question 6

Choline can activate

Answer 6

alpha 7 nAChR

Question 7

alpha7 nAChR characteristics

Answer 7

more permeable to calcium, desensitize quickly (only permit few ions to travel), are expressed in human bronchial epithelial cells, aortic endothelials cells and human skin keratinocytes
and can be activated by choline (degradation product of ACh)

Question 8

what is alpha-bungarotoxin

Answer 8

a-BTX is a competitive, relatively irreversible inhibitor of of muscle and alpha-7 nAChR subtypes

Question 9

What enzyme is responsible for ACh synthesis?

Answer 9

Choline Acetyltransferase

Question 10

what are the effects of ACh on the airways (receptor, effector cell, disease)

Answer 10

ACh activates the muscarinic AChR on airway smooth muscl and mucus producing cells to cause bronchoconstriction and mucus secretion in asthma and COPD

Question 11

what are emerging effects of ACh on airways?

Answer 11

inflammation, proliferation, fibrosis, airway remodeling

Question 12

Acetycholine is released from what type of cell?

Answer 12

ACh is released by parasympathetic nerves as a neurotransmitter and by epithelial and inflammatory cells as a paracrine or autocrine hormone

Question 13

bronchoconstriction and mucus secretion are regulated by what signaling mechanism?

Answer 13

parasympathetic NS is responsible for muscarinic control of bronchoconstriction and mucus secretion via
ACh signlaing to –>Gq coupled M1, M3 receptors
and ———————>Gi couples M2 receptors

Question 14

Where are M1 receptors located?

Answer 14

at the ganglion in the postganglionic nerve, is common in exocrine glands and in the CNS.

Question 15

Where are M2 receptors located?

Answer 15

prejunctional (are autoinhibitory bc recall they are Gi coupled)

Question 16

function of M1 and M3 receptors?

Answer 16

involved in mucus, electrolyte and water secretion by submucosal glands

Question 17

function of M3 receptors

Answer 17

mediate bronchoconstriction on airway smooth muscle

Question 18

How is obstructive vs restrictive airway disease distinguished?

Answer 18

Obstructive lung diseases include conditions that make it hard to exhale all the air in the lungs (COPD, asthma, CF). People with restrictive lung disease have difficulty fully expanding their lungs with air (interstitial lung disease, ALS-neuromuscular disease)

Question 19

anticholinergic therapy mechanism

Answer 19

inhibits muscarinic M3 receptor: ipratropium, oxitropium (shortacting) and tioptropium (long acting)

Question 20

mainstay treatment for COPD

Answer 20

anticholinergic

Question 21

mainstay treatment for asthma

Answer 21

short acting Beta-2 agonist and then anticholinergic (less effective)
However for uncontrolled acute asthma, beta 2 agonist +ipratoprium improves lung functions and decreases hospital admissions

Question 22

combo treatments for asthma

Answer 22

glycopyronium + indacaterol; tiotropium +olodaterol; umeclidinium + vilanterol

once daily muscarinic antagonist + B2 agonist

goal: to simplify drug regimen and improved lung function over 24 h period