Abstract

The effects of cholecystokinin octapeptide (CCK8), bombesin and manganese (Mn 2+) on phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis were studied in AR42J cells. One-half maximal stimulation of inositol monophosphate (InsP1) accumulation occurred at either 5 nM CCK8 or 5 nM bombesin, and maximal stimulation occurred at 30 nM for each agonist. Mn 2+ did not alter basal PIP2 hydrolysis. However, addition of Mn 2+ 5 min prior to stimulation with either CCK8 or bombesin for 60 min significantly attenuated [ 3H]InsP1 accumulation. Following brief periods of incubation with CCK8 (15 sec) Mn 2+ significantly reduced inositol tris- and tetrakisphosphate accumulation. These data suggest that Mn 2+ may participate in the regulation of CCK8- and bombesin-mediated generation of phosphoinositides.

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