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Adenylate cyclase type 2 Potassium- transporting ATPase subunit beta Potassium- transporting ATPase alpha chain 1 Muscarinic acetylcholine receptor M3 Gastrin Gastrin/cholecystokinin type B receptor Carbonic anhydrase 1 Histamine H2 receptor Guanine nucleotide- binding protein G(s) subunit alpha isoforms short Gβ Guanine nucleotide- binding protein G(I)/G(S)/G(O) subunit gamma-12 Guanine nucleotide- binding protein G(s) subunit alpha isoforms short Adenylate cyclase type 2 Guanine nucleotide- binding protein G(s) subunit alpha isoforms short Gβ Guanine nucleotide- binding protein G(I)/G(S)/G(O) subunit gamma-12 Gβ Guanine nucleotide- binding protein G(I)/G(S)/G(O) subunit gamma-12 Histamine Histamine Histamine H2 receptor Histamine H2 receptor Histamine cAMP Acetylcholine Inositol 1,4,5-trisphosphate Nizatidine Histamine GTP GDP Adenosine triphosphate PPi H2O CO2 HCO3- H+ ATP H2O K+ ADP Pi H+ K+ Magnesium Zinc (II) ion GDP GTP Magnesium GTP Guanine nucleotide- binding protein G(s) subunit alpha isoforms short GTP Gq Signalling Pathway Stomach Lumen Cytosol Basolateral Membrane Apical Membrane Enterochromaffin-like Cell Gastric Parietal Cell Stomach Lumen Nizatidine is absorbed in the GI tract after being taken orally and is delivered to the stomach epithelium through the blood. Nizatidine reversibly binds to the histamine H2 receptor blocking histamine. Normally after histamine binds, Gs is activated and activates adenylate cyclase type 2 to form a complex with it. Because Nizatidine is inhibiting the activation, the signalling cascade does not proceed and Gs doesn't form a complex with adenylate cyclase. The adenylate cyclase-Gs complex after being activated works to convert adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). Nizatidine's inhibition prevents this conversion and low concentrations of cAMP are formed. cAMP is partially responsible for activating the potassium-hydrogen ATPase transporter which pumps hydrogen ions into the stomach lumen. Low levels of cAMP lower the activity of this pump so less hydrogen ions are secreted. Hydrogen ions are produced from the conversion of carbon dioxide into bicarbonate. Acetylcholine and gastrin can still activate the potassium-hydrogen ATPase pump, but overall the amount acidity of the stomach lumen is decreased. Enterochromaffin-like cells are along the stomach epithelium as well. They produce histamine which is released through exocytotic vesicles to bind to their neighbouring parietal cells. Histamine is released from enterochromaffin-like cells from cellular pools from gastrin release stimulation. Parietal Cell
ADCY2 ATP4B ATP4A CHRM3 Unknown CCKBR CA1 HRH2 GNAS GNB1 GNG12 GNAS ADCY2 GNAS GNB1 GNG12 GNB1 GNG12 Histamine Histamine HRH2 HRH2 Histamine cAMP Acetylcholine Inositol 1,4,5- trisphosphate Nizatidine Histamine Guanosine triphosphate Guanosine diphosphate Adenosine triphosphate Pyrophosphate Water Carbon dioxide Hydrogen carbonate Hydrogen Ion Adenosine triphosphate Water Potassium Adenosine diphosphate Phosphate Hydrogen Ion Potassium Guanosine diphosphate Guanosine triphosphate Guanosine triphosphate GNAS Guanosine triphosphate Gq Signalling Pathway
ADCY2 ATP4B ATP4A CHRM3 CCKBR CA1 HRH2 GNAS GNB1 GNG12 GNAS ADCY2 GNAS GNB1 GNG12 GNB1 GNG12 Hsm Hsm HRH2 HRH2 Hsm cAMP ACh Inotp Nizatid Hsm GTP GDP ATP PPi H2O CO2 HCO3- H+ ATP H2O K+ ADP Pi H+ K+ Mg2+ Zinc GDP GTP Mg2+ GTP GNAS GTP Gq Si P Stomach Lumen Cytosol Basolateral Membrane Apical Membrane Enterochromaffin-like Cell Gastric Parietal Cell Stomach Lumen Nizatidine is absorbed in the GI tract after being taken orally and is delivered to the stomach epithelium through the blood. Nizatidine reversibly binds to the histamine H2 receptor blocking histamine. Normally after histamine binds, Gs is activated and activates adenylate cyclase type 2 to form a complex with it. Because Nizatidine is inhibiting the activation, the signalling cascade does not proceed and Gs doesn't form a complex with adenylate cyclase. The adenylate cyclase-Gs complex after being activated works to convert adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). Nizatidine's inhibition prevents this conversion and low concentrations of cAMP are formed. cAMP is partially responsible for activating the potassium-hydrogen ATPase transporter which pumps hydrogen ions into the stomach lumen. Low levels of cAMP lower the activity of this pump so less hydrogen ions are secreted. Hydrogen ions are produced from the conversion of carbon dioxide into bicarbonate. Acetylcholine and gastrin can still activate the potassium-hydrogen ATPase pump, but overall the amount acidity of the stomach lumen is decreased. Enterochromaffin-like cells are along the stomach epithelium as well. They produce histamine which is released through exocytotic vesicles to bind to their neighbouring parietal cells. Histamine is released from enterochromaffin-like cells from cellular pools from gastrin release stimulation. Parietal Cell
ADCY2 ATP4B ATP4A CHRM3 CCKBR CA1 HRH2 GNAS GNB1 GNG12 GNAS ADCY2 GNAS GNB1 GNG12 GNB1 GNG12 Hsm Hsm HRH2 HRH2 Hsm cAMP ACh Inotp Nizatid Hsm GTP GDP ATP Ppi H2O CO2 HCO3 H+ ATP H2O K+ ADP Pi H+ K+ GDP GTP GTP GNAS GTP Gq Si P