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Myosin light chain kinase, smooth muscle PKA complex PKA complex Guanine nucleotide- binding protein G(s) subunit alpha isoforms short 5- hydroxytryptamine receptor 4 Myosin LC-P Myosin light chain 3 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 Adenylate cyclase type 5 Calmodulin Voltage- dependent calcium channel subunit alpha-2/delta-1 Prucalopride Ca+ K+ K+ Ca+ GDP GTP ATP cAMP PPi Pi Pi Ca+ Muscle Contraction Muscle Relaxation Magnesium Calcium Manganese Cytosol Smooth Muscle Myocyte 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. High PKA activity leads to increased phosphorylation of certain proteins, including myosin light chain (MLC), in smooth muscle cells. Increased MLC phosphorylation promotes the activation of myosin light chain kinase (MLCK). There is an overall increase in calcium levels in the cytosol. Increased calcium is able to bind readily to calmodulin. The activation of myosin light chain kinase activates the synthesis of Myosin LC-P which leads to a high concentration of myosin light chain and muscle contraction Myosin binds from actin causing sarcomere filaments to slide resulting in muscle contraction Actin Myosin Prucalopride binds to 5-HT 4 receptors that activate Gs signalling to cause smooth muscle contraction in the gastrointestinal tract. Prucalopride is administered orally As cAMP levels increase, the levels of phosphorylated proteins involved in contraction increase, leading to higher intracellular calcium concentration. Gastrointestinal tract blood vessel
MYLK PRKAR1A PRKAR2A GNAS HTR4 MYL3 MYL3 CACNB1 CACNA1C PPP1CB CALM1 KCNN4 ADCY5 CALM1 CACNA2D1 Prucalopride Calcium Potassium Potassium Calcium Guanosine diphosphate Guanosine triphosphate Adenosine triphosphate cAMP Pyrophosphate Phosphate Phosphate Calcium Muscle Contraction Muscle Relaxation
MYLK PRKAR1A PRKAR2A GNAS HTR4 MYL3 MYL3 CACNB1 CACNA1C PPP1CB CALM1 KCNN4 ADCY5 CALM1 CACNA2D1 Pruca Ca+ K+ K+ Ca+ GDP GTP ATP cAMP PPi Pi Pi Ca+ Mus Con Mus Rel Mg2+ Ca2+ Mn2+ Cytosol Smooth Muscle Myocyte 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. High PKA activity leads to increased phosphorylation of certain proteins, including myosin light chain (MLC), in smooth muscle cells. Increased MLC phosphorylation promotes the activation of myosin light chain kinase (MLCK). There is an overall increase in calcium levels in the cytosol. Increased calcium is able to bind readily to calmodulin. The activation of myosin light chain kinase activates the synthesis of Myosin LC-P which leads to a high concentration of myosin light chain and muscle contraction Myosin binds from actin causing sarcomere filaments to slide resulting in muscle contraction Actin Myosin Prucalopride binds to 5-HT 4 receptors that activate Gs signalling to cause smooth muscle contraction in the gastrointestinal tract. Prucalopride is administered orally As cAMP levels increase, the levels of phosphorylated proteins involved in contraction increase, leading to higher intracellular calcium concentration. Gastrointestinal tract blood vessel
MYLK PRKAR1A PRKAR2A GNAS HTR4 MYL3 MYL3 CACNB1 CACNA1C PPP1CB CALM1 KCNN4 ADCY5 CALM1 CACNA2D1 Pruca Ca2+ K+ K+ Ca2+ GDP GTP ATP cAMP Ppi Pi Pi Ca2+ Mus Con Mus Rel