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-response curve for histamine-induced [3H]inositol monophosphate ([3H]IP1) accumulation in slices of rat cerebral cortex prelabelled with [3H]inositol. Dithiothreitol had no significant effect on carbachol-induced [3H]IP1 accumulation. The effect of dithiothreitol appeared to be at the level of the H1-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]IP1 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]IP1 accumulation in human HeLa cells was also potentiated by dithiothreitol, but the decrease in the EC50 was only 3-fold. It is suggested that differences in the magnitude of the effect of dithiothreitol on histamine H1-receptor mediated responses between tissues may reflect in part the position of the concentration-response curve in the absence of dithiothreitol.
Young
K W
KW
Department of Pharmacology, University of Cambridge, UK.
Young
J M
JM
D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D046508:Culture Techniques; D004229:Dithiothreitol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism
D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D006165:Guanylyl Imidodiphosphate; D006632:Histamine; D002217:Carbachol; D011738:Pyrilamine; D004229:Dithiothreitol