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Pathway Description
Oxytocin Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2021-08-22
Last Updated: 2023-10-25
Oxytocin is a recombinant hormone used to induce or strengthen uterine contractions in pregnant women to aid in labor and delivery or to control postpartum bleeding. Administration of exogenous oxytocin is indicated in the antepartum period to initiate or improve uterine contractions for vaginal delivery in situations where there is fetal or maternal concern. Oxytocin is produced in the hypothalamus and is secreted from the paraventricular nucleus to the posterior pituitary where it is stored. It is then released in pulses during childbirth to induce uterine contractions. The concentration of oxytocin receptors on the myometrium increases significantly during pregnancy and reaches a peak in early labor. Activation of the oxytocin receptor on the myometrial cell leading to activation of the Gq signaling cascade. Gq signaling cascade activates phospholipase C which produces inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate. IP3 activates IP3 receptor on the sarcoplasmic reticulum, leading to calcium moving from the sarcoplasmic reticulum to the cytosol, increasing cytosolic calcium concentration. Calcium also enters the cell through the L-type calcium channel on the cell membrane, which is activated downstream after activation of the oxytocin receptor. Calcium binds to calmodulin activating myosin light chain kinase, leading to phosphorylation of myosin light chain. Phosphorylated myosin light chain binds to actin to form an actinomyosin complex which causes smooth muscle contraction. DAG activates protein kinase C (PKC). PKC activates mitogen-activated protein kinase (MAPK), which activates phospholipase A2, leading to prostaglandin synthesis. Prostaglandins like prostaglandin E2 stimulates uterine muscle contraction. PKC may also promote muscle contraction by phosphorylating CPI-17, the regulatory subunit of myosin light chain phosphatase. Additionally, the transforming protein rhoA is activated with activation of the oxytocin receptor. Transforming protein rhoA activates rho-associated protein kinase. Rho-associated protein kinase also phosphorylates CPI-17. Phosphorylation of myosin light chain phosphatase inactivates it, preventing this enzyme from converting myosin-LC-P to myosin-LC. Myosin-LC causes smooth muscle relaxation. Therefore, by inhibiting myosin light chain phosphatase, the concentration of myosin-LC-P increases and the concentration of myosin-LC decreases, further promoting uterine muscle contraction.
References
Oxytocin Pathway References
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