TY - JOUR T1 - INFLAMMATION INDUCED BY HISTAMINE, SEROTONIN, BRADYKININ AND COMPOUND 48/80 IN THE RAT: ANTAGONISTS AND MECHANISMS OF ACTION JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 300 LP - 310 VL - 191 IS - 2 AU - Harriet M. Maling AU - Marion E. Webster AU - Martha A. Williams AU - Wilford Saul AU - William Anderson, Jr. Y1 - 1974/11/01 UR - http://jpet.aspetjournals.org/content/191/2/300.abstract N2 - A number of antagonists were tested for their ability to inhibit the inflammation induced by subplantar injection into the rat hindpaw of histamine, serotonin, bradykinin or compound 48/80. Triprolidine and chlorpheniramine specifically inhibited histamine-induced edema. D-2-Bromolysergic acid diethylamide and methysergide specifically inhibited serotonin-induced edema. Tripelennamine, pyrilamine, promethazine, antazoline, diphenhydramine, phenindamine, chlorcyclizine and l-isoproterenol inhibited the edemas induced by either serotonin or histamine. Promethazine, antazoline, diphenhydramine and l-isoproterenol also partially blocked the edema induced by bradykinin. Cyproheptadine inhibited the edemas induced by both serotonin and bradykinin. Carboxypeptidase B and soybean trypsin inhibitor did not reduce significantly the edemas induced by histamine, serotonin or bradykinin. By means of specific antagonists, the edema induced by compound 48/80 was shown to be due to the release of serotonin (65%) and histamine (30%). Kinins are probably not involved. In doses as low as 0.005 µmol/kg s.c., l-isoproterenol inhibited compound 48/80-induced edema. Some antihistamines, especially tripelennamine, inhibited compound 48/80 edema more effectively than could be explained by their inhibition of either histamine or serotonin. Their effectiveness was correlated with their abilities to inhibit the release of mediators from isolated rat peritoneal mast cells. © 1974 by The Williams & Wilkins Co. ER -