Low Concentrations Of Indomethacin Research Articles

EFFECT OF INDOMETHACIN AND RELATED DRUGS ON THE CALCIUM ION‐DEPENDENT SECRETION OF LYSOSOMAL AND OTHER ENZYMES BY NEUTROPHIL POLYMORPHONUCLEAR LEUCOCYTES In vitro

1 Rabbit isolated peritoneal neutrophil polymorphonuclear leucocytes were depleted of calcium by exposure for 1 h to calcium-free bathing fluid at 4 degrees C. 2 Addition of calcium ions to the previously calcium-depleted calls during incubation at 37 degrees C stimulated the release of beta-glucuronidase and of lysozyme but not of lactate dehydrogenase. 3 Low concentrations of indomethacin, flufenamate or salicylate, such as those which occur in the blood plasma after therapeutic doses of these drugs, selectively inhibited the calcium-induced release of beta-glucuronidase. The slight release of this enzyme which occurred in the absence of added calcium ions was not altered by these drugs, neither was the release of lactate dehydrogenase. 4 Release of lysozyme was inhibited by low concentrations of salicylate, amidopyrine or oxyphenbutazone, independent of the presence or absence of calcium ions. 5 Chloroquine, hydrocortisone or colchicine did not alter the release of leucocyte enzymes.

Antagonism of tone and prostaglandin-mediated responses in a tracheal preparation by indomethacin and SC-19220.

1 The effects of the prostaglandin synthetase inhibitor, indomethacin and the prostaglandin antagonist SC-19220 (1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f) (1,4)oxazepine-10-carbonyl] hydrazine), were examined on the tone of the guinea-pig isolated tracheal preparation and on the responses of the preparation to prostaglandin F(2alpha), arachidonic acid and methacholine.2 Indomethacin (0.05-1.6 mug/ml) produced a long-lasting inhibition of the intrinsic tone of the tracheal preparation and of the contractile responses to arachidonic acid. Much higher concentrations of indomethacin also reduced the responses of the preparation to methacholine. This effect was readily reversible and appeared to be unrelated to the action on tone.3 The contractile responses of the preparation to prostaglandin F(2alpha) were enhanced by low concentrations of indomethacin (1-5 mug/ml) and inhibited by higher concentrations (2.5-80 mug/ml).4 SC-19220 was shown to inhibit responses of the preparation to prostaglandin F(2alpha) in concentrations (0.1-1 mug/ml) which had no effect on responses to methacholine. Similar concentrations also inhibited the intrinsic tone of the preparation and the responses to arachidonic acid.5 The evidence suggests that prostaglandins may be involved in the maintenance of tone of the guinea-pig isolated tracheal preparation.