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

• Published in: Japanese Journal of Pharmacology Vol. 73; no. 3; pp. 197 - 205
• Main Author: Warashina, Akira
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Japanese Pharmacological Society 1997
• Subjects: Adrenal chromaffin cell (rat); Adrenal Medulla - cytology; Adrenal Medulla - drug effects; Adrenal Medulla - metabolism; Animals; Arachidonic Acid - metabolism; Arachidonic Acid - toxicity; Bradykinin; Bradykinin - pharmacology; Calcium - metabolism; Catecholamine secretion; Catecholamines - metabolism; Chromaffin Granules - drug effects; Chromaffin Granules - metabolism; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - metabolism; Dinoprostone - toxicity; Dose-Response Relationship, Drug; Drug Synergism; Fluorescent Dyes - chemistry; Histamine - pharmacology; Ibuprofen - pharmacology; Indoles - chemistry; Indomethacin; Indomethacin - administration & dosage; Indomethacin - pharmacology; Male; Muscarine; Muscarine - pharmacology; Muscarinic Agonists - pharmacology; Nicotine - pharmacology; Oxytocics - metabolism; Oxytocics - toxicity; Potassium - metabolism; Rats; Rats, Wistar; Muscarine; Catecholamine secretion; Indomethacin; Adrenal chromaffin cell (rat); Bradykinin
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.73.197

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.