title: Potentiation by indomethacin of receptor-mediated catecholamine secretion in rat adrenal medulla.
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.
authors.affiliation: Department of Physiology, Niigata University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Warashina
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000633:toxicity; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005456:Fluorescent Dyes / Q000737:chemistry; D006632:Histamine / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010120:Oxytocics / Q000378:metabolism / Q000633:toxicity; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002395:Catecholamines; D016861:Cyclooxygenase Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D018721:Muscarinic Agonists; D010120:Oxytocics; D016718:Arachidonic Acid; D009538:Nicotine; D009116:Muscarine; D006632:Histamine; D015232:Dinoprostone; C048960:indo-1; D011188:Potassium; D001920:Bradykinin; D002118:Calcium; D007052:Ibuprofen; D007213:Indomethacin