Fructose 2,6-bisphosphate levels and modulation of glycolysis by histamine, cholecystokinin, and forskolin in isolated rabbit gastric glands

Abstract

In isolated rabbit gastric glands incubated in the presence of 1 mmol/L glucose, the content of fructose 2,6-bisphosphate (F-2,6-P 2) was 5.7 ± 0.5 pmol/mg dry weight. This value was progressively incremented by increasing glucose concentration in the incubation medium, and was almost doubled at 10 mmol/L glucose. Under these conditions, a close correlation could be established between the levels of F-2,6-P 2 and the rate of l-lactate formation ( r = .98; P < .05). Both histamine (0.1 mmol/L) and cholecystokinin octapeptide (CCK-OCT; 0.1 μmol/L) increased l-lactate production, without significant changes in either F-2,6-P 2 concentration or the amount of 6-phosphofructo-2-kinase in active form. In contrast, forskolin, which markedly increased the glandular content of cyclic adenosine monophosphate (cAMP), partially blocked glucose consumption and caused a significant reduction in both F-2,6-P 2 levels and the proportion of 6-phosphofructo-2-kinase in active form. Furthermore, forskolin partially blocked the rate of glucose uptake by isolated gastric glands. Our results suggest a regulatory role of F-2,6-P 2 in the control of the glycolytic flux in response to glucose, but not in its response to histamine or CCK-OCT.