Abstract
Amitriptyline, at a concentration of 10(-4) M, significantly inhibited the release of histamine from purified peritoneal rat mast cells in response to compound 48/80, but was without effect upon the output of 5-HT. The reduction was not extensive, and concentrations of the drug above or below 10(-4) M were without effect. Amitriptyline (10(-8)-10(-4) M) inhibited uptake of exogenous 5-HT in a concentration dependent manner. Paradoxically, however, histamine uptake was significantly increased in the presence of this drug, but only at a concentration of 10(-4) M. This effect was observed at 4 degrees C for both amines. Concentrations of amitriptyline in excess of 10(-4) M caused lysis of the mast cells. These results suggest that the observed selective inhibitory effect of amitriptyline upon histamine output may be a function of altered amine uptake rather than differential inhibition and 5-HT secretion.
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