Potentiation by 1,4-dithiothreitol of histamine-induced inositol phosphate formation in rat cerebral cortex and human HeLa cells

Abstract

Dithiothreitol (1 mM) caused a 340-fold shift of the concentration-response curve for histamine-induced [ 3H]inositol monophosphate ([ 3H]IP 1) accumulation in slices of rat cerebral cortex prelabelled with [ 3H]inositol. Dithiothreitol had no significant effect on carbachol-induced [ 3H]IP 1 accumulation. The effect of dithiothreitol appeared to be at the level of the H 1-receptor, since curves of histamine inhibition of [ 3H]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 potentiation of [ 3H]IP 1 accumulation. The small shift of the curve of histamine inhibition of [ 3H]mepyramine binding by a stable GTP analogue, 5′-guanylylimidodiphosphate, was not increased in the presence of dithiothreitol. Histamine-induced [ 3H]IP 1 accumulation in human HeLa cells was also potentiated by dithiothreitol, but the decrease in the EC 50 was only 3-fold. It is suggested that differences in the magnitude of the effect of dithiothreitol on histamine H 1-receptor mediated responses between tissues may reflect in part the position of the concentration-response curve in the absence of dithiothreitol.