Somatostatin-14 (SS) significantly increased inositol-1,4,5-trisphosphate (IP3) accumulation in rat hypothalamic, striatal, frontoparietal cortical and hippocampal slices. However, this stimulation of IP3 accumulation by SS was highest in the frontoparietal cortex and hippocampus. The effect was already significant with 0.01 mu M in the frontoparietal cortex (P<0.05) and hippocampus (P<0.05) and the maximal accumulation was evident with 0.1 mu M SS, in all areas studied. A concentration of 1 mu M SS, lacked this effect in hypothalamus and striatum. SS rapidly increased IP3 accumulation in all brain areas studied. This effect was maximal at 15 s of incubation and decreased subsequently. At 60 s incubation, levels were still elevated in frontoparietal cortex and hippocampus but had returned to basal values in hypothalamus and striatum. Somatostatin-28 (SS-28) and the SS analogues, D-Trp(8)-D-Cys(14) and SMS 201-995, also significantly stimulated IP3 accumulation although the effect of SMS 201-995 was greater than that of SS in the striatum in comparison with controls (P<0.001 and P<0.01, respectively). These results suggest that SS action at the hypothalamus, striatum, frontoparietal cortex and hippocampus is mediated at least in part by the accumulation of IP3, which may initiate intracellular processes responsible for some biological SS effects.