Differential effects of elevated calcium ion concentrations on inositol phospholipid responses in mouse and rat cerebral cortical slices.

Inositol phospholipid turnover in cerebral cortical slices from mouse and rat was assessed using a [3H]inositol pre-labelling technique followed by anion exchange chromatography to isolate [3H]inositol phosphates ([3H]InsP chi). In both mouse and rat cerebral cortical slices, elevating the CaCl2 concentration of the Krebs medium from 1.3 to 4 mM did not significantly enhance the accumulation of [3H]InsP chi in the absence of any stimulus, or in the presence of glutamate (3 mM), depolarizing concentrations of KCl (25 mM), 5-hydroxytryptamine (0.3 mM), the calcium ionophore A23187 (33 microM) or carbachol (1 mM). However, the accumulations of [3H]InsP chi induced by histamine (1 mM) or noradrenaline (0.1 mM) were significantly increased by between 95 and 178% in cerebral cortical slices from both species by the elevation of extracellular calcium. Analysis of the individual inositol phosphates revealed that elevated ambient calcium enhanced the histamine-generated accumulations of [3H]InsP2, [3H]InsP3 and [3H]InsP4 by up to two-fold, while only the [3H]InsP3 response to carbachol was significantly increased. Under the same conditions, histamine, but not carbachol, selectively increased the accumulation of [3H]PtdInsP2 by up to 50%. The [3H]InsP chi responses to histamine and noradrenaline in combination with the calcium ionophore A23187 were greater-than-additive, inferring an enhancement of the receptor response by raised intracellular calcium. However, the combination of A23187 with glutamate or KCl resulted in significantly less-than-additive [3H]InsP chi responses. The [3H]InsP chi response to carbachol or 5-hydroxytryptamine was not significantly altered in the presence of A23187. Taken together, these results indicate heterogeneity between the mechanisms of inositol phospholipid turnover induced by these various stimuli in mammalian cerebral cortical slices.