Effects of histamine-trifluoromethyl-toluidide derivative (HTMT) on intracellular calcium in human lymphocytes.

We have studied the effects of histamine trifluoromethyl-toluidide derivatives on calcium mobilization in human peripheral blood lymphocytes using spectrofluorometric analysis. HTMT (compound 1) induced two phases of increase in intracellular calcium concentration--a rapid intracellular calcium concentration peak (10-60 sec), partial recovery (1-3 min) and a sustained moderate elevation that persisted for more than 5 min. The EC50 value was 1.9 X 10(-5) M. Pretreatment of lymphocytes with the agonist resulted in receptor desensitization that recovered after 15 min when the cells were drug free. The presence of extracellular ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid did not abrogate the early phase of the calcium rise, suggesting that the calcium appearing in the cytosol during the early phase was derived from intracellular stores. The increase in intracellular calcium concentration by this compound was competitively antagonized by high concentrations of histamine but not by classic histamine receptor antagonists (H1, H2 or H3). Other cyclic AMP elevating agents, with the exception of prostaglandin E2, did not affect the increase in calcium levels induced by compound 1. Compound 1 caused phosphatidylinositol metabolism resulting in inositol phosphate production, suggesting that inositol triphosphate may be the second messenger for the mobilization of intracellular Ca2+ by compound 1. The data imply a specific binding site for histamine trifluoromethyl toluidide derivative on lymphocytes that is different than the classic H1, H2 or H3 receptors.