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Pathway Description
Oxybutynin Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2022-04-07
Last Updated: 2023-10-25
Oxybutynin is an antimuscarinic agent that relaxes the muscles of the bladder, and prevents the urge to void. This helps with conditions such as bladder spasms and overactive bladder syndrome (OABS).
Oxybutynin is an agonist of muscarinic acetylcholine receptors subtype M1, M2, and M3. In the bladder muscles, M2 and M3 are present in a 3 to 1 concentration. However, it has been found that the M2 muscarinic acetylcholine receptors are not involved in the contraction of the bladder. Therefore the inhibition of M3 muscarinic acetylcholine receptors is the receptor oxybutynin inhibits to treat OABS or any bladder overactive problems. M2 receptors have been shown to activate smooth muscle contractions by decreasing the probability of potassium channels opening or opening non-specific cation channels which would cause an influx of calcium. Then the inhibition of M2 muscarinic channels would cause smooth muscle relaxation.However, the M3 receptor is still found to be the major cause of muscle contraction in the bladder.
Muscarinic acetylcholine receptors M3 are coupled to the Gq signaling cascade. The activation of this leads to the acitvation of phospholipase C, which converts Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 activates IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. DAG activates protein kinase C (PKC). One of the downstream effects of PKC include activation of calcium channels on the membrane, leading to influx of calcium ions into the cytosol. Both IP3 and DAG increase cytosolic levels of calcium which then binds to calmodulin to create a calcium-calmodulin complex. Muscle contraction and relaxation are controlled by the enzymes myosin kinase and myosin phosphatase. Myosin kinase phosphorylates myosin light chain, leading to interaction between actin and myosin, producing muscle contraction. Myosin phosphorylase dephosphorylates the phosphorylated myosin light chain, preventing interaction with actin, producing muscle relaxation. The calcium-calmodulin activates myosin kinase, leading to increased phosphorylation of myosin light chain and more muscle contraction. Oxybutynin can be administered as an oral tablet or syrup.
References
Oxybutynin Pathway References
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