Potentiation by Indomethacin of Receptor-Mediated Catecholamine Secretion in Rat Adrenal Medulla

[摘要] References(29)Cited-By(2)Effects of indomethacin on catecholamine secretion evoked by receptor agonists, muscarine, bradykinin or histamine, in rat adrenal chromaffin cells were studied. Indomethacin at 200 μM increased a sustained component of secretion during stimulation with muscarine, bradykinin and histamine by a factor of 2.3, 2.1 and 2.9, respectively, whereas it did not significantly alter basal, high-K+ and nicotine-evoked secretions. Although indomethacin at above 400 μM dose-dependently increased basal secretion, the amount of secretion induced by indomethacin alone was much smaller than that in muscarine-evoked secretion as compared at the same concentration of indomethacin applied. Bradykinin-evoked secretion and its potentiation by indomethacin were not inhibited by 20 μM nifedipine but were suppressed by 0.5 mM Ni2+. The cyclooxygenase inhibitor, ibuprofen (200 μM)did not mimic the effect of indomethacin; prostaglandin E2 (20 μM)and arachidonic acid (100 μM)did not significantly alter either bradykinin-evoked secretion itself or its potentiation by indomethacin. Bradykinin increased the intracellular free Ca2+ concentration, [Ca2+]i, in cells loaded with indo-1, and this response was enhanced in the presence of indomethacin. These results suggest that indomethacin may promote Ca2+ entry to potentiate agonist-evoked catecholamine secretions through a novel action that is not directly related to the inhibition of cyclooxygenase activity with indomethacin.

[学科分类] 药理学

[关键词] Adrenal chromaffin cell (rat);Catecholamine secretion;Indomethacin;Muscarine;Bradykinin