THE EFFECTS OF DRUGS ON THE UPTAKE OF AMINES BY MAST CELLA

Abstract

Neoplastic mast cells, taken from an ascitic tumour in mice and incubated in vitro, took up ¹⁴C-labelled 5-hydroxytryptamine and histamine from the medium. Uptake during the first hour gave an approximate measure of the initial rate. The amount of each amine taken up in this time was determined by bioassay and by radioactivity, the two methods giving similar results. The curves obtained by plotting initial rate of uptake against concentration in the medium suggested that the uptake of 5-hydroxytryptamine was by an active process and also by diffusion, whereas uptake of histamine was by diffusion only. The cells also took up ¹⁴C-labelled (±)-noradrenaline and tryptamine, apparently by diffusion. The active uptake of 5-hydroxytryptamine was inhibited by lowering the temperature to 25° C or by increasing the pH to 8.9, procedures which had little effect on histamine uptake. The effects of cocaine, imipramine, chlorpromazine, mepyramine, promethazine, phenoxybenzamine, lysergic acid diethylamide, bromolysergic acid diethylamide, methysergide, guanethidine, dichloroisoprenaline and pronethalol on the uptake of amines were examined. In general, any antagonist which inhibited uptake of 5-hydroxytryptamine had little effect on uptake of histamine, and vice versa. Possible ways in which these antagonists produce their effects on amine uptake are discussed. A high concentration of 5-hydroxytryptamine, of tryptamine or of noradrenaline inhibited uptake of histamine, but only tryptamine decreased uptake of 5-hydroxytryptamine. These results, together with those from experiments with antagonists, suggest that there are specific binding sites for 5-hydroxtryptamine in these cells.