The activity of amitriptyline as a differential inhibitor of amine secretion from rat peritoneal mast cells: The contribution of amine uptake

Amitriptyline, at a concentration of 10^-4M, 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^-4M were without effect. Amitriptyline (10^-8-10^-4M) 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^-4M. This effect was observed at 4°C for both amines. Concentrations of amitriptyline in excess of 10^-4M 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.