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Beta-endorphin N-type calcium channel potassium voltage-gated channel subfamily J Adenylate cyclase type 2 Gq protein signaling cascade Phospholipase C Inositol 1,4,5- trisphosphate receptor type 1 Protein kinase C alpha type 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 Myosin light chain kinase, smooth muscle Muscarinic acetylcholine receptor M3 Soluble guanylyl cyclase Myosin light chain phosphatase Intermediate conductance calcium- activated potassium channel protein 4 Myosin LC-P Myosin light chain 3 Calmodulin-1 Mu-type opioid receptor Guanine nucleotide- binding protein G(i) subunit alpha-1 Calmodulin-1 Inositol 1,4,5-trisphosphate Acetylcholine NO Cyclic GMP Trimebutine Trimebutine Ca+ cAMP Ca+ Ca+ Na+ Na+ Acetylcholine Ca+ Ca+ NO K+ K+ Trimebutine Trimebutine ATP PPi Phosphatidylinositol 4,5-bisphosphate GTP GTP Ca+ Diacylglycerol Analgesia Muscle Contraction Muscle Relaxation Magnesium Magnesium Calcium Calcium Manganese Decreased calcium levels lead to decreased neurotransmitter release. Less acetylcholine is released from synaptic vesicles The mu opioid receptor through the gamma subunit inhibits voltage gated N-type calcium channels stopping the influx of calcium into the neuron. The Gi subunit of the mu opioid receptor activates the inwardly rectifying potassium channel increasing K+ conductance. This causes membrane hyperpolarization decreasing the chances of neuronal firing/action potential. Myenteric Plexus Neuron Synapse Trimebutine binds to mu-type opioid receptors in the myenteric plexus large intestines Cytoplasm Synaptic Vesicle Sarcoplasmic Reticulum Decreased calcium is unable to bind readily to calmodulin so it does not activate myosin light chain kinase There is an overall decrease in calcium levels in the cytosol Cytosol Intestinal Smooth Muscle Cell Nitric oxide is not inhibited and activates Guanylyl cyclase so cyclic GMP can activate Myosin light hain phosphatase which causes the muscle to relax. Myosin light chain kinase is activated less often which leads to a decrease in Myosin LC-P. This causes the muscle to contract less often. The decreased release of acetylcholine causes a decrease in activation of muscarinic receptors on the smooth muscles of the intestine Trimebutine binds to L type calcium channels blocking calcium influx Decreased calcium levels means calcium activated potassium channels cannot be activated Actin Myosin Actin and myosin unbind allowing filaments to slide and relaxation to occur Trimebutine is administered as an oral tablet
Vacuole Unknown CACNB1 KCNJ9 ADCY2 GNAQ PLCB1 ITPR1 PRKCA CACNA1A CACNB1 CACNA2D2 MYLK CHRM3 GUCY1A2 PPP1CB KCNN4 MYL3 MYL3 CALM1 OPRM1 GNAI1 GNB1 GNG2 CALM1 Inositol 1,4,5- trisphosphate Acetylcholine Nitric oxide Cyclic GMP Trimebutine Trimebutine Calcium cAMP Calcium Calcium Sodium Sodium Acetylcholine Calcium Calcium Nitric oxide Potassium Potassium Trimebutine Trimebutine Adenosine triphosphate Pyrophosphate Phosphatidylinositol 4,5- bisphosphate Guanosine triphosphate Guanosine triphosphate Calcium Diacylglycerol Analgesia Muscle Contraction Muscle Relaxation