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Myosin light chain kinase, smooth muscle Adenylyl Cyclase PKA complex PKA complex Protein kinase C beta-3 adrenergic receptor G protein complex Myosin LC-P Myosin light chain 3 Inositol 1,4,5- trisphosphate receptor type 1 Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent L-type calcium channel subunit alpha-1C Myosin light chain phosphatase Calmodulin Intermediate conductance calcium- activated potassium channel protein 4 Phospholipase C Guanine nucleotide- binding protein alpha Calmodulin Guanine nucleotide- binding protein G(I)/G(S)/G(T) subunit beta-1 Guanine nucleotide- binding protein G(I)/G(S)/G(O) subunit gamma-12 Voltage- dependent calcium channel subunit alpha-2/delta-1 Mirabegron Ca+ Ca+ Ca+ K+ K+ Mirabegron GDP GTP ATP cAMP Inositol 1,4,5-trisphosphate Phosphatidylinositol 4,5-bisphosphate Diacylglycerol GTP Pi Pi Pi Calcium Ca+ Muscle Contraction Muscle Relaxation Magnesium Calcium Manganese Sarcoplasmic Reticulum Cytosol Detrusor Smooth Muscle Cell Mirabegron binds to beta-3 adrenergic receptor. It is administered as an oral tablet. The G protein complex separates into alpha and beta/gamma subunits. GDP is replaced with GTP on the alpha subunit. Activated PKA can phosphorylate calcium activated potassium channels causing potassium efflux and promoting hyperpolarization. Activated PKA phosphorylates the IP3 receptor to reduce its affinity for IP3. Activated PKA phosphorylates phospholipase C. There is an overall decrease in calcium levels in the cytosol. Decreased calcium is unable to bind readily to calmodulin. The inhibition of myosin light chain kinase prevents the synthesis of Myosin LC-P which leads to a high concentration of myosin light chain and muscle relaxation. Myosin unbinds from actin causing the sarcomere filaments to slide resulting in muscle relaxation. Actin Filament Myosin Filament
MYLK ADCY9 PRKAR1A PRKAR2A PRKCA GPR109B GNB1 MYL3 MYL3 ITPR1 CACNB1 CACNA1C PPP1CB CALM1 KCNN4 PLCB1 GNAS CALM1 GNB1 GNG12 CACNA2D1 Mirabegron Calcium Calcium Calcium Potassium Potassium Mirabegron Guanosine diphosphate Guanosine triphosphate Adenosine triphosphate cAMP Inositol 1,4,5- trisphosphate Phosphatidylinositol 4,5- bisphosphate Diacylglycerol Guanosine triphosphate Phosphate Phosphate Phosphate Calcium Muscle Contraction Muscle Relaxation