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Beta-endorphin Adenylate cyclase type 2 Voltage- dependent L-type calcium channel subunit beta-1 G protein- activated inward rectifier potassium channel 3 Mu-type opioid receptor Gβ Gγ Neuronal acetylcholine receptor subunit beta-2 Acetylcholine Eluxadoline Na+ Acetylcholine Na+ Ca+ Ca+ Na+ Na+ ATP cAMP PPi Eluxadoline GTP Neuronal acetylcholine receptor subunit alpha-4 nAchR Smooth Muscle Contraction Guanine nucleotide- binding protein G(i) subunit alpha-1 Magnesium Less nicotinic acetylcholine receptors are actiavted. Contraction of GI muscle is reduced, motility and secretion decreases. Neuromuscular Junction Smooth Muscle Myocyte Decreased calcium levels lead to decreased neurotransmitter release. Less acetylcholine is available in the synapse to bind to post synaptic muscarinic receptors on the muscle. Eluxadoline activates mu opioid receptors inhibiting the N-type calcium channels on the neuron. This prevents calcium to enter the neuron and depolarize. Mu opioid receptor is coupled to Go and Gi proteins. When diphenoxylate activates the mu opioid receptor, the Gi cascade causes inhibition of adenylate cyclase and the Go signaling pathway causes inhibition of Ca2+ channels and activation of K+ channels. Pre-Synaptic Neuron Cytosol With the inhibition of adenylate cyclase, it is unable to synthesize cAMP which further prevents calcium from entering the neuron and depolarization of the neuron Synaptic Vesicle K+ channel is activated allowing K+ to enter the neuron and sodium to leave the neuron. This results in hyperpolarization, reducing the ability of the neuron to fire. Eluxadoline is taken orally
Unknown ADCY2 CACNB1 KCNJ9 OPRM1 GNB1 GNG2 Unknown Acetylcholine Eluxadoline Sodium Acetylcholine Sodium Calcium Calcium Sodium Sodium Adenosine triphosphate cAMP Pyrophosphate Eluxadoline Guanosine triphosphate Unknown nAchR Smooth Muscle Contraction GNAI1
ADCY2 CACNB1 KCNJ9 OPRM1 GNB1 GNG2 ACh Eluxa Na+ ACh Na+ Ca+ Ca+ Na+ Na+ ATP cAMP PPi Eluxa GTP