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How does acetylcholine mediate its parasympathetic effects?

I'm really confused because I keep finding contradictory things on this. I know that it is supposed to cause parasympathetic effects, which include a decreased heart rate and blood pressure. However, my notes also say that the muscarinic M1/3/5 receptors cause an increase in Ca2+ and muscle contraction, and therefore that would mean they'd cause an increase in BP? There's a whole diagram here showing how it works through the IP3 pathway. I've read other things online that it causes its parasympathetic effects through other ways such as NO and increased K+... but none of these ways really mention the whole IP3 pathway causing increased calcium?

Thank you for your time :smile:
Original post by monica95
I'm really confused because I keep finding contradictory things on this. I know that it is supposed to cause parasympathetic effects, which include a decreased heart rate and blood pressure. However, my notes also say that the muscarinic M1/3/5 receptors cause an increase in Ca2+ and muscle contraction, and therefore that would mean they'd cause an increase in BP? There's a whole diagram here showing how it works through the IP3 pathway. I've read other things online that it causes its parasympathetic effects through other ways such as NO and increased K+... but none of these ways really mention the whole IP3 pathway causing increased calcium?

Thank you for your time :smile:


Think of the parasympathetic system as the 'rest and digest' system, whereas the sympathetic system as the 'fight or flight' system. You are correct in that the muscarinic M1/3/5 receptors are Gq-coupled receptors that activate phospholipase C to increase IP3 levels, which ultimately releases sarcoplasmic stores of Ca2+, leading to muscle contraction. However, you need to remember where anatomically these receptors are located. The M3 receptor is mainly found in smooth muscle in the gastrointestinal tract, where it stimulates peristalsis, the smooth muscle of the bladder, where it stimulates voiding, iris smooth muscle causing miosis, in the salivary glands increasing saliva production, and in the bronchioles causing bronchoconstriction.

You also need to bear in mind that the M2 receptor is a Gi/o-coupled receptor that inhibits adenylyl cyclase, decreasing intracellular cAMP levels. This is predominantly found in the heart, e.g. at the SA and AV nodes, where they decrease electrical activity and heart rate.

If you take anything away from this, just learn that the context of the situation is very important. Although muscle contraction may occur, you need to think 1) where anatomically, 2) which relevant receptors are present there, and 3) what is its physiological role.

Hope this helps.
Reply 2
Original post by thegodofgod
Think of the parasympathetic system as the 'rest and digest' system, whereas the sympathetic system as the 'fight or flight' system. You are correct in that the muscarinic M1/3/5 receptors are Gq-coupled receptors that activate phospholipase C to increase IP3 levels, which ultimately releases sarcoplasmic stores of Ca2+, leading to muscle contraction. However, you need to remember where anatomically these receptors are located. The M3 receptor is mainly found in smooth muscle in the gastrointestinal tract, where it stimulates peristalsis, the smooth muscle of the bladder, where it stimulates voiding, iris smooth muscle causing miosis, in the salivary glands increasing saliva production, and in the bronchioles causing bronchoconstriction.

You also need to bear in mind that the M2 receptor is a Gi/o-coupled receptor that inhibits adenylyl cyclase, decreasing intracellular cAMP levels. This is predominantly found in the heart, e.g. at the SA and AV nodes, where they decrease electrical activity and heart rate.

If you take anything away from this, just learn that the context of the situation is very important. Although muscle contraction may occur, you need to think 1) where anatomically, 2) which relevant receptors are present there, and 3) what is its physiological role.

Hope this helps.


Awhh thank you so much for taking the time to thoroughly explain that for me! I completely get it now, thank you very much 😊 x*
Original post by monica95
Awhh thank you so much for taking the time to thoroughly explain that for me! I completely get it now, thank you very much 😊 x*


No problems, glad you found it useful! :smile:

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