Tachikawa E, Kondo Y, Takahashi S, Kashimoto T, Mizuma K
Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan.
Res Commun Chem Pathol Pharmacol. 1993 Jul;81(1):3-14.
The effects of the antiallergic drugs, oxatomide, ibudilast, and tranilast on catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine were examined. Both oxatomide (2-100 microM) and ibudilast (10-100 microM) resulted in the inhibition of the secretion of catecholamines from the cells in a concentration-dependent manner, whereas tranilast (100 nM-100 microM) did not. Oxatomide and ibudilast also reduced the acetylcholine-induced 45Ca2+ influx into the cells. The concentration-response curves for oxatomide and ibudilast inhibiting 45Ca2+ influx were quite similar to those for drugs inhibiting the secretion. Oxatomide similarly reduced both high K(+)-induced 45Ca2+ influx and secretion. However, the oxatomide inhibition of acetylcholine-induced secretion was not overcome by increasing the concentrations of acetylcholine or Ca2+. Oxatomide also inhibited histamine-induced secretion and the inhibition was almost overcome by increasing histamine concentration. These results indicate that oxatomide and ibudilast inhibit catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine. The inhibition is due to the suppression of Ca2+ influx into the cells through voltage-dependent Ca2+ channels. The results further suggest that oxatomide competitively antagonizes histamine receptors and inhibits the secretion stimulated by histamine.
研究了抗组胺药奥沙米特、异丁司特和曲尼司特对乙酰胆碱刺激牛肾上腺嗜铬细胞分泌儿茶酚胺的影响。奥沙米特（2 - 100微摩尔/升）和异丁司特（10 - 100微摩尔/升）均以浓度依赖性方式抑制细胞儿茶酚胺的分泌，而曲尼司特（100纳摩尔/升 - 100微摩尔/升）则无此作用。奥沙米特和异丁司特还减少了乙酰胆碱诱导的45Ca2+流入细胞。奥沙米特和异丁司特抑制45Ca2+流入的浓度 - 反应曲线与抑制分泌的药物曲线非常相似。奥沙米特同样减少了高钾诱导的45Ca2+流入和分泌。然而，增加乙酰胆碱或Ca2+的浓度并不能克服奥沙米特对乙酰胆碱诱导分泌的抑制作用。奥沙米特还抑制组胺诱导的分泌，增加组胺浓度几乎可以克服这种抑制作用。这些结果表明，奥沙米特和异丁司特抑制乙酰胆碱刺激牛肾上腺嗜铬细胞分泌儿茶酚胺。这种抑制是由于通过电压依赖性Ca2+通道抑制Ca2+流入细胞。结果进一步表明，奥沙米特竞争性拮抗组胺受体并抑制组胺刺激的分泌。
