how does ACh cause contraction in the GI tract?
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.
- 1 decade agoFavorite Answer
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
cAMP leads to phosphorylation/activation of Protein Kinase A
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
These active G-proteins activate the enzyme Phospholipase C
Phospholipase C cleaves IP3 from membrane phospholipids
IP3 diffuses into the cell and encounters the sarcoplasmic reticulum (SR)
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
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