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Myosin light chain kinase, smooth muscle Adenylate cyclase type 9 cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit Protein kinase C alpha type Beta-2 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 Intermediate conductance calcium- activated potassium channel protein 4 Phospholipase C Guanine nucleotide- binding protein alpha Calmodulin-1 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 Norepinephrine Ca+ Ca+ K+ K+ Ca+ Norepinephrine 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 Vascular Smooth Muscle Cell Norepinephrine binds to beta-2 adrenergic receptor. 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 leading to muscle relaxation. Dilation Actin Filament Myosin Filament Droxidopa is administered as an oral tablet and then converted to norepinephrine via decarboxylation
MYLK ADCY9 PRKAR1A PRKAR2A PRKCA ADRB2 GNB1 MYL3 MYL3 ITPR1 CACNB1 CACNA1C PPP1CB KCNN4 PLCB1 GNAS CALM1 GNB1 GNG12 CACNA2D1 Norepinephrine Calcium Calcium Potassium Potassium Calcium Norepinephrine 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