Akira Warashina
Department of Physiology, Niigata University School of Medicine, Niigata
951, Japan
Abstract: Effects of indomethacin on catecholamine secretion
evoked by receptor agonists, muscarine, bradykinin or histamine, in rat
adrenal chromaffin cells were studied. Indomethacin at 200 microM 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 microM 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 microM nifedipine
but were suppressed by 0.5 mM Ni2+. The cyclooxygenase inhibitor, ibuprofen
(200 microM) did not mimic the effect of indomethacin; prostaglandin E2
(20 microM) and arachidonic acid (100 microM) 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.
Keywords: Adrenal chromaffin cell (rat), Catecholamine secretion, Indomethacin,
Muscarine, Bradykinin