TY - JOUR T1 - Roles of Extracellular Ca<sup>++</sup> and Calmodulin in Roxatidine-Stimulated Secretion and Synthesis of Mucus by Cultured Rabbit Gastric Mucosal Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 37 LP - 42 VL - 284 IS - 1 AU - Satoru Takahashi AU - Susumu Okabe Y1 - 1998/01/01 UR - http://jpet.aspetjournals.org/content/284/1/37.abstract N2 - 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 increase 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 μM, 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. The American Society for Pharmacology and Experimental Therapeutics ER -