title: Roles of extracellular Ca++ and calmodulin in roxatidine-stimulated secretion and synthesis of mucus by cultured rabbit gastric mucosal cells.
abstract: We found that roxatidine stimulates mucus secretion and synthesis by cultured rabbit gastric mucosal cells. In this study, we examined the roles of the extracellular Ca++ and calmodulin in these effects of roxatidine. Reduction of the extracellular Ca++ concentration decreased the roxatidine-induced increases in mucus secretion and synthesis by gastric mucosal cells. Roxatidine concentration-dependently promoted Ca++ influx and caused an increases in intracellular Ca++. After the addition of roxatidine, the increases in the secretion and synthesis reflected those in Ca++ influx and intracellular Ca++ concentration and then disappeared as Ca++ influx and intracellular Ca++ concentration returned to the control level. The roxatidine-stimulated Ca++ influx and intracellular Ca++ mobilization were abolished by reduction of the extracellular Ca++ concentration. Nifedipine and diltiazem inhibited both the effects of roxatidine, but even at 10 microM, the inhibition was partial. Furthermore, W-7 (a calmodulin antagonist) completely abolished the effects of roxatidine on mucus secretion and synthesis without causing a reduction of the stimulated Ca++ influx. Taken together, these results suggest that roxatidine promotes Ca++ influx through both voltage-sensitive Ca++ channels and other Ca++ entry gates and the subsequent intracellular Ca++ mobilization, leading to potentiation of mucus secretion and synthesis by rabbit gastric mucosal cells. In addition, Ca(++)-activated calmodulin may play a pivotal role in these stimulatory effects of roxatidine.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Okabe
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D009093:Mucus / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D006635:Histamine H2 Antagonists; D010880:Piperidines; D013449:Sulfonamides; C017967:W 7; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; C053742:roxatidine acetate