how does ACh cause contraction in the GI tract?

Question

How does ACh cause contraction in the GI tract / ileum (in a guinea pig)?

i know it binds to muscurinic receptors. M3 receptors but does it bind to M2 aswell.

How does it cause contraction by binding to the M3 and M2 receptors? i ave researched but i cannot find a simple version so can someone break it down for me into steps or something.

Confused :-/

Answer 1

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Take a look at this paper: Sanders, K. M. Am J Physiol Gastrointest Liver Physiol 275: G1-G7, 1998;

Condensing from this paper...

M2 and M3 muscarinic receptors are present in GI smooth muscle in a ratio of 80% to 20%. These will affect two pathways related to smooth muscle contraction. First, the pathways in question:

Pathway 1: cAMP-mediated inhibition of contraction:

Adenylyl cyclase converts ATP to cAMP

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cAMP leads to phosphorylation/activation of Protein Kinase A

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Active Protein Kinase A appears to "short circuit" muscle contraction by opening some potassium and calcium channels at once. (It's kinda complicated but it's all in the paper.)

Pathway 2: IP3-mediated calcium release (stimulates contraction):

G-proteins at the membrane (specifically Gq/11 type) are activated by a receptor and bind to GTP

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These active G-proteins activate the enzyme Phospholipase C

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Phospholipase C cleaves IP3 from membrane phospholipids

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IP3 diffuses into the cell and encounters the sarcoplasmic reticulum (SR)

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IP3 binds to calcium channels on the SR and releases calcium, causing muscle contraction.

So how do these relate to M2 and M3 receptors?

M2 receptors control inhibitory G-proteins (Gi/Go). When the receptors bind ACh, their G-proteins inhibit adenylyl cyclase. The adenylyl cyclase pathway prevents muscle contraction. The M2 turns off the pathway, allowing muscle contraction.

M3 receptors are bound to Gq/11 type G-proteins. When ACh binds to M3, these G-proteins activate phospholipase C and turn on contraction via IP3-mediated calcium release.

Source(s): Sanders, K. M. Am J Physiol Gastrointest Liver Physiol 275: G1-G7, 1998

Answer 2

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