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Gq protein signaling cascade Phospholipase C Inositol 1,4,5- trisphosphate receptor type 3 Myosin light chain kinase, smooth muscle Protein kinase C Mitogen- activated protein kinase 1 Mitogen- activated protein kinase 3 Cytosolic phospholipase A2 Transforming protein RhoA Rho-associated protein kinase 1 Gq protein signaling cascade Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 D(1A) dopamine receptor Myosin light chain 3 Calmodulin-1 Myosin LC-P Myosin light chain phosphatase CPI-17 CPI-17-P Myosin light chain phosphatase-P Actin, cytoplasmic 1 Calmodulin-1 Actin, cytoplasmic 1 Myosin light chain 3 Inositol 1,4,5-trisphosphate Methylergonovine Ca+ Ca+ Ca+ Ca+ Methylergonovine Phosphatidylinositol 4,5-bisphosphate Magnesium Calcium Magnesium Magnesium Manganese Manganese Ca+ Diacylglycerol Muscle Relaxation Prostaglandin Synthesis Muscle Contraction Calcium Calcium Myometrial Cell Sarcoplasmic Reticulum Cytosol Methylergometrine acts directly on the smooth muscle of the uterus through binding and antagonism of D1 receptors Gq signaling cascade activates phospholipase C which produces IP3 and DAG 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 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 Muscle contraction The RhoA protein and protein kinase C can also lead to the inactivated, phosphorylated form of myosin light chain phosphatase, preventing the conversion of myosin-LC-P to Myosin-LC Protein kinase C leads to prostaglandin synthesis. Prostaglandins like E2 stimulates uterine contraction Methylergometrine is taken orally and absorbed from the gastrointestinal tract passive diffusion blood vessel Uterus Actin Filament Myosin Filament Methylergometrine increases the tone rate and amplitude of rhythmic contractions thus shortens third stage of labour and reduces blood loss Myosin binds to actin causing the sarcomere filaments to key into each other resulting in muscle contractility.