Effects of antiallergic drugs on catecholamine secretion from bovine adrenal chromaffin cells.
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.
Tachikawa
E
E
Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan.
Kondo
Y
Y
Takahashi
S
S
Kashimoto
T
T
Mizuma
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*; D007212:Indolizines; D011720:Pyrazoles
D000109:Acetylcholine; D001993:Bronchodilator Agents; D002118:Calcium; D002395:Catecholamines; D006634:Histamine H1 Antagonists; D010879:Piperazines; D011725:Pyridines; D062367:ortho-Aminobenzoates; C012293:tranilast; C015408:oxatomide; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles