BL-5255 II: effects on release and smooth muscle activity of mediators of immediate hypersensitivity reactions.
BL-5255 inhibited release of preformed mediators from passively sensitized mast cells in the rat peritoneal cavity, chopped monkey lung or human lung tissue. The compound failed to block rat cutaneous reactions elicited by histamine or serotonin. It exhibited weak to no ability, depending on the mediator employed, to block contraction of isolated guinea pig ileum or tracheal tissue. At concentrations of 1 microM or greater, BL-5255 itself was contractile to the ileum but not to the quiescent or submaximally contracted trachea. The compound relaxed spontaneously contracting rabbit jejunum muscle but at doses not likely to be achieved in vivo. Phosphodiesterase activities in extracts of rat and human lung were inhibited at concentrations greater than those required to inhibit mediator release.
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D008168:Lung / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010323:Passive Cutaneous Anaphylaxis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D011744:Pyrimidinones; D011968:Receptors, Histamine; D011985:Receptors, Serotonin; C021943:BL 5255