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Myosin light chain kinase, smooth muscle 5- hydroxytryptamine receptor 1B Guanine nucleotide- binding protein G(i) subunit alpha-1 Guanine nucleotide- binding protein G(I)/G(S)/G(T) subunit beta-1 Adenylate cyclase type 5 PKA complex PKA complex Myosin LC-P Myosin light chain 3 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 Serine/threonine- protein phosphatase PP1-beta catalytic subunit Calmodulin-1 Calmodulin-1 cAMP Dihydroergotamine Ca+ Ca+ ATP ATP PPi Ca+ Muscle Contraction Muscle Relaxation Vasoconstriction Magnesium Calcium Manganese Myosin binds from actin causing the sarcomere filaments to slide leading to smooth muscle contraction and vasoconstriction Increased calcium binds readily to calmodulin to activate myosin light chain kinase Reduced protein kinase A (PKA) activity is generally associated with increased intracellular calcium concentration and the activation of myosin light chain kinase (MLCK), all of which contribute to smooth muscle contraction and blood vessel constriction. Cytosol Activation of myosin light chain kinase leads to high concentration of myosin LC-P which causes contractions of the muscles Vascular Smooth Muscle Cell Constriction Dihydroergotamine is an agonist at 5-HT1B, 1D, 1F receptors present on intracranial blood vessels and peripheral terminals of the trigeminal nerve innervating cranial blood vessels Actin Filament Myosin Filament Dihydroergotamine is administered as an oral pill Lower PKA activity leads to decreased phosphorylation of certain proteins, including myosin light chain (MLC), in smooth muscle cells. Reduced MLC phosphorylation promotes the activation of myosin light chain kinase (MLCK). Decreased cAMP levels can lead to increased intracellular calcium concentration by various mechanisms, including the release of calcium from intracellular stores. Cranial blood vessels Brain
MYLK HTR1B GNAI1 GNB1 GNG2 ADCY5 PRKAR1A PRKAR2A MYL3 MYL3 CACNA1A CACNB1 CACNA2D2 PPP1CB CALM1 CALM1 cAMP Dihydroergotamine Calcium Calcium Adenosine triphosphate Adenosine triphosphate Pyrophosphate Calcium Muscle Contraction Muscle Relaxation Vasoconstriction