POTENTIATION BY 1,4-DITHIOTHREITOL OF HISTAMINE-INDUCED INOSITOL PHOSPHATE FORMATION IN RAT CEREBRAL-CORTEX AND HUMAN HELA-CELLS

Dithiothreitol (1 mM) caused a 340-fold shift of the concentration-res ponse curve for histamine-induced [H-3]inositol monophosphate ([H-3]IP 1) accumulation in slices of rat cerebral cortex prelabelled with [H-3 ]inositol. Dithiothreitol had no significant effect on carbachol-induc ed [H-3]IP1, accumulation. The effect of dithiothreitol appeared to be at the level of the H-1-receptor, since curves of histamine inhibitio n of [H-3]mepyramine binding to a membrane fraction from rat cerebral cortex were shifted to lower concentrations by dithiothreitol, with a similar concentration-dependence for dithiothreitol as observed for po tentiation of (IH)-H-3]IP1, accumulation. The small shift of the curve of histamine inhibition of [H-3]mepyramine binding by a stable GTP an alogue, 5'-guanylylimidodiphosphate, was not increased in the presence of dithiothreitol. Histamine-induced [H-3]IP1 accumulation in human H eLa cells was also potentiated by dithiothreitol, but the decrease in the EC(50) was only 3-fold. It is suggested that differences in the ma gnitude of the effect of dithiothreitol on histamine H-1-receptor medi ated responses between tissues may reflect in part the position of the concentration-response curve in the absence of dithiothreitol.